Parrish, K M; Higuchi, S; Muramatsu, T; Stinson, F S; Harford, T C
In Japan, per capita alcohol consumption increased sharply during the post World War II period followed by an increase in cirrhosis mortality. The prevalence of alcoholic cirrhosis among hospitalized patients also increased, from 11% in 1969 to 18% in 1985. Despite an increase in the percentage of drinkers among young women, over 80% of women in Japan are still abstainers or light drinkers. Thus, female cirrhosis mortality rates can be used as a proxy measure of non-alcohol-related cirrhosis mortality rates to estimate alcohol-related cirrhosis deaths among Japanese men. Employing this method, we conclude that two-thirds of cirrhosis deaths among men between 24 and 85 years of age and half of all cirrhosis deaths were attributable to alcohol. Two factors are probably responsible for the differences in proportional morbidity and proportional mortality of alcohol-related cirrhosis: differences in survival rates between alcoholic and non-alcoholic cirrhosis patients and detection bias toward post-hepatic cirrhosis. The synergistic effect of alcohol on viral hepatitis may in part explain excess cirrhosis deaths among Japanese men.
Yoon, Young-Hee; Yi, Hsiao-ye; Thomson, Patricia C.
Background Hispanics have much higher cirrhosis mortality rates than non-Hispanic Blacks and Whites. Although heavy alcohol use and hepatitis C virus (HCV) infection are two major risk factors for cirrhosis, no studies have systematically assessed the contribution of alcohol- and HCV-related cirrhosis deaths to the total cirrhosis mortality for Hispanics as a whole and its variations across Hispanic subgroups. To fill this gap, the current study presents the latest data on total cirrhosis mortality as well as its component alcohol- and HCV-related cirrhosis mortality for all Hispanics and for Hispanic subgroups. Methods The multiple-cause approach was used to analyze data from the U.S. Multiple Cause of Death Data Files for 28,432 Hispanics and 168,856 non-Hispanic Whites (as a comparison group) who died with cirrhosis as the underlying or a contributing cause during 2000–2004. Four major Hispanic subgroups were defined by national origin or ancestry, including Mexicans, Puerto Ricans, Cubans, and Other Hispanics. The cirrhosis deaths were divided into four distinctive cause-of-death categories: alcohol-related, HCV-related, both alcohol- and HCV-related, and neither alcohol- nor HCV-related. Age-adjusted total cirrhosis death rates and percentage shares of the cause-specific categories were compared across Hispanic subgroups and non-Hispanic Whites. Results Compared with non-Hispanic Whites, all Hispanic subgroups except Cubans had much higher cirrhosis mortality. The age-adjusted total cirrhosis death rates were twice as high for Puerto Ricans and Mexicans as for non-Hispanic Whites. Alcohol-related and HCV-related cirrhosis death rates also were higher for most Hispanic subgroups than for non-Hispanic Whites. Conclusions Heavy alcohol use and hepatitis C viral infection are two important factors contributing to the high cirrhosis mortality among Hispanics. However, their relative contributions to total cirrhosis mortality varied by gender and Hispanic subgroup
Lamis, Dorian A.; Malone, Patrick S.
This study examined the relations among alcohol-related problems, perceived burdensomeness, thwarted belongingness, and suicide proneness in undergraduate college students (N = 996). As hypothesized, alcohol-related problems, perceived burdensomeness, and thwarted belongingness were all significantly and positively correlated with suicide proneness. The relation between experiencing alcohol-related problems and suicide proneness was, in part, accounted for by perceived burdensomeness and thwarted belongingness. Additionally, the mediation via perceived burdensomeness was significantly stronger than the mediation via thwarted belongingness. Results suggest that it would be advisable for clinicians to be aware of students’ experiences with alcohol-related problems in conjunction with their levels of burdensomeness and belongingness when assessing for suicide risk PMID:21883409
Miller, Cameron A; Parrott, Dominic J; Giancola, Peter R
This study investigated the mediating effect of trait aggressivity on the relation between agreeableness and alcohol-related aggression in a laboratory setting. Participants were 116 healthy male social drinkers between 21 and 30 years of age. Agreeableness and trait aggressivity were measured using the Big Five Inventory and the Buss-Perry Aggression Questionnaire, respectively. Following the consumption of an alcohol or no-alcohol control beverage, participants completed a modified version of the Taylor Aggression Paradigm, in which electric shocks were received from and administered to a fictitious opponent during a competitive task. Aggression was operationalized as the proportion of the most extreme shocks delivered to the fictitious opponent under conditions of low and high provocation. Results indicated that lower levels of agreeableness were associated with higher levels of trait aggressivity. In turn, higher levels of trait aggressivity predicted extreme aggression in intoxicated, but not sober, participants under low, but not high, provocation. Findings highlight the importance of examining determinants of intoxicated aggression within a broader theoretical framework of personality.
Liver cirrhosis; Chronic liver disease; End-stage liver disease; Liver failure - cirrhosis; Ascites - cirrhosis ... Cirrhosis is the end result of chronic liver damage caused by ... liver disease in the United States are: Hepatitis B or hepatitis ...
Hustad, John T P; Pearson, Matthew R; Neighbors, Clayton; Borsari, Brian
After high school, college students escalate their drinking at a faster rate than their noncollege-attending peers, and alcohol use in high school is one of the strongest predictors of alcohol use in college. Therefore, an improved understanding of the role of predictors of alcohol use during the critical developmental period when individuals transition to college has direct clinical implications to reduce alcohol-related harms. We used path analysis in the present study to examine the predictive effects of personality (e.g., impulsivity, sensation seeking, hopelessness, and anxiety sensitivity) and three measures of alcohol perception: descriptive norms, injunctive norms, and perceptions regarding the perceived role of drinking in college on alcohol-related outcomes. Participants were 490 incoming freshmen college students. Results indicated that descriptive norms, injunctive norms, and the role of drinking largely mediated the effects of personality on alcohol outcomes. In contrast, both impulsivity and hopelessness exhibited direct effects on alcohol-related problems. The perceived role of drinking was a particularly robust predictor of outcomes and mediator of the effects of personality traits, including sensation seeking and impulsivity on alcohol outcomes. The intertwined relationships observed in this study between personality factors, descriptive norms, injunctive norms, and the role of drinking highlight the importance of investigating these predictors simultaneously. Findings support the implementation of interventions that target these specific perceptions about the role of drinking in college.
Hustad, John T. P.; Pearson, Matthew R.; Neighbors, Clayton; Borsari, Brian
After high school, college students escalate their drinking at a faster rate than their noncollege-attending peers, and alcohol use in high school is one of the strongest predictors of alcohol use in college. Therefore, an improved understanding of the role of predictors of alcohol use during the critical developmental period when individuals transition to college has direct clinical implications to reduce alcohol-related harms. We used path analysis in the present study to examine the predictive effects of personality (e.g., impulsivity, sensation seeking, hopelessness, and anxiety sensitivity) and three measures of alcohol perception: descriptive norms, injunctive norms, and perceptions regarding the perceived role of drinking in college on alcohol-related outcomes. Participants were 490 incoming freshmen college students. Results indicated that descriptive norms, injunctive norms, and the role of drinking largely mediated the effects of personality on alcohol outcomes. In contrast, both impulsivity and hopelessness exhibited direct effects on alcohol-related problems. The perceived role of drinking was a particularly robust predictor of outcomes and mediator of the effects of personality traits, including sensation seeking and impulsivity on alcohol outcomes. The intertwined relationships observed in this study between personality factors, descriptive norms, injunctive norms, and the role of drinking highlight the importance of investigating these predictors simultaneously. Findings support the implementation of interventions that target these specific perceptions about the role of drinking in college. PMID:24467197
Cirrhosis is scarring of the liver. Scar tissue forms because of injury or long-term disease. Scar ... the blood, help digest food and store energy. Cirrhosis can lead to Easy bruising or bleeding, or ...
Buckner, Julia D; Terlecki, Meredith A
Social anxiety disorder more than quadruples the risk of developing an alcohol use disorder, yet it is inconsistently linked to drinking frequency. Inconsistent findings may be at least partially due to lack of attention to drinking context - it may be that socially anxious individuals are especially vulnerable to drinking more often in specific contexts that increase their risk for alcohol-related problems. For instance, socially anxious persons may drink more often while alone, before social situations for "liquid courage" and/or after social situations to manage negative thoughts about their performance. Among current (past-month) drinkers (N=776), social anxiety was significantly, positively related to solitary drinking frequency and was negatively related to social drinking frequency. Social anxiety was indirectly (via solitary drinking frequency) related to greater past-month drinking frequency and more drinking-related problems. Social anxiety was also indirectly (via social drinking frequency) negatively related to past-month drinking frequency and drinking-related problems. Findings suggest that socially anxious persons may be vulnerable to more frequent drinking in particular contexts (in this case alone) and that this context-specific drinking may play an important role in drinking problems among these high-risk individuals.
Pearson, Matthew R; Hustad, John T P
The present study examined three alcohol-perception variables (descriptive norms, injunctive norms, and college-related alcohol beliefs) as mediators of the predictive effects of four personality traits (impulsivity, sensation seeking, anxiety sensitivity, and hopelessness) on alcohol use and alcohol-related consequences in a sample of mandated college students (n=875). Our findings replicated several findings of a previous study of incoming freshman college students (Hustad et al., in press) in that impulsivity and hopelessness had direct effects on alcohol-related problems, sensation seeking and impulsivity had indirect effects on alcohol-related outcomes via college-related alcohol beliefs, and college-related alcohol beliefs predicted both alcohol use and alcohol-related problems. We discuss the implications of our findings for global college student interventions as well as personality-targeted interventions.
Shang, Haitao; Wang, Zhijun; Song, Yuhu
Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury. In cirrhotic liver where hepatocytes proliferation is compromised, liver progenitor cells (LPCs) are activated and then differentiated into hepatocytes and cholangiocytes, leading to the generation of regenerative nodules and functional restoration. Here, we summarize and discuss recent findings on the mechanisms underlying LPCs-mediated regeneration in liver cirrhosis. Firstly, we provide recent research on the mechanism underlying LPCs activation in severe or chronic liver injury. Secondly, we present new and exciting data on exploring the origin of LPCs, which reveal that the hepatocytes give rise to duct-like progenitors that then differentiate back into hepatocytes in chronic liver injury or liver cirrhosis. Finally, we highlight recent findings from the literature exploring the role of LPCs niche in directing the behavior and fate of LPCs. This remarkable insight into the cellular and molecular mechanisms of LPCs-mediated regeneration in liver cirrhosis will provide a basis for translating this knowledge into clinical application.
Patock-Peckham, Julie A.; Morgan-Lopez, Antonio A.
Objective: Depression is often found to be comorbid with alcohol-related problems. Parental overprotection, which may be of particular importance during emerging adulthood, has been linked to internalizing symptoms in offspring. This article evaluates the impact of parenting styles and parental confidence in their offspring on an internalizing pathway to alcohol-related problems through self-esteem and depression. Method: Mediational links were tested among parenting styles (authoritative, authoritarian, permissive), parental confidence (overprotection, autonomy), self-esteem, depression, and alcohol-related problems. A two-group, multiple indicator multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. Results: Overall, having a father who was confident in his child's ability to make autonomous decisions was protective against depression for both genders. Perceptions of paternal autonomy mediated the impact of the fathers' parenting styles (authoritative, permissive) on depression for both genders. For men, parental overprotection mediated the impact of an authoritarian father on self-esteem, and self-esteem mediated the impact of parental overprotection on depression. Moreover, among men, perceptions of maternal autonomy mediated the impact of the mothers' parenting styles (authoritative, permissive) on self-esteem, and self-esteem mediated the impact of maternal autonomy on depression. Conclusions: The current pattern of findings is distinct from pathways through behavioral undercontrol with influences from the same-sex parent for both genders. These findings indicate that parenting may have differential influences on internalizing pathways to alcohol-related problems. PMID:19261233
Lamis, Dorian A.; Malone, Patrick S.
The relationship among alcohol-related problems, perceived burdensomeness, thwarted belongingness, and suicide proneness in undergraduate college students (N = 996) was examined. As hypothesized, alcohol-related problems, perceived burdensomeness, and thwarted belongingness were all significantly and positively correlated with suicide proneness.…
Angkaw, Abigail C; Haller, Moira; Pittman, James O E; Nunnink, Sarah E; Norman, Sonya B; Lemmer, Jennifer A; McLay, Robert N; Baker, Dewleen G
Veterans returning from Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) have been found to be at increased risk for post-traumatic stress disorder (PTSD) and alcohol use disorders, leading to negative mental health-related quality of life (MHRQoL). The current study examined the unique impact of alcohol consumption levels versus alcohol-related consequences on the relationship between PTSD symptoms and MHRQoL in a sample of OEF/OIF combat veterans (N = 205, median age 29, 95% men). Mediation analyses indicated that the effect of PTSD symptoms on MHRQoL was explained only by alcohol-related consequences and not by alcohol consumption. Findings highlight the importance of including alcohol-related consequences in clinical assessment and intervention programs for OEF/OIF veterans. Additionally, this study enhances knowledge regarding the underlying mechanisms of functional impairment related to PTSD and alcohol use disorders.
Ibáñez, Manuel I.; Camacho, Laura; Mezquita, Laura; Villa, Helena; Moya-Higueras, Jorge; Ortet, Generós
Personality and expectancies are relevant psychological factors for the development of adolescent alcohol use and misuse. The present study examined their direct, mediated and moderated effects on different drinking behaviors in adolescence. Personality domains of the five-factor model, positive and negative alcohol expectancies (AEs), alcohol use during the week and the weekend, and alcohol-related problems were assessed in a sample of 361 adolescents. Different personality dimensions were directly associated with specific alcohol outcomes: Extraversion, low Conscientiousness and low Openness were associated with weekend alcohol use; low Agreeableness was related to weekday use; whereas low Agreeableness, low Conscientiousness and Extraversion were associated with alcohol-related problems. In addition, positive AEs mediated the relationship between Extraversion and alcohol use, whereas both positive and negative expectancies mediated the association between Neuroticism and alcohol consumption and alcohol-related problems. Finally, both types of expectancies interacted with Extraversion to predict alcohol problems. Our results highlight the importance of examining the complex interplay of comprehensive personality models and AEs to gain a better understanding of the development of different alcohol use and misuse patterns in adolescence. PMID:26635714
Ibáñez, Manuel I; Camacho, Laura; Mezquita, Laura; Villa, Helena; Moya-Higueras, Jorge; Ortet, Generós
Personality and expectancies are relevant psychological factors for the development of adolescent alcohol use and misuse. The present study examined their direct, mediated and moderated effects on different drinking behaviors in adolescence. Personality domains of the five-factor model, positive and negative alcohol expectancies (AEs), alcohol use during the week and the weekend, and alcohol-related problems were assessed in a sample of 361 adolescents. Different personality dimensions were directly associated with specific alcohol outcomes: Extraversion, low Conscientiousness and low Openness were associated with weekend alcohol use; low Agreeableness was related to weekday use; whereas low Agreeableness, low Conscientiousness and Extraversion were associated with alcohol-related problems. In addition, positive AEs mediated the relationship between Extraversion and alcohol use, whereas both positive and negative expectancies mediated the association between Neuroticism and alcohol consumption and alcohol-related problems. Finally, both types of expectancies interacted with Extraversion to predict alcohol problems. Our results highlight the importance of examining the complex interplay of comprehensive personality models and AEs to gain a better understanding of the development of different alcohol use and misuse patterns in adolescence.
O’Brien, Alastair J.; Fullerton, James N.; Massey, Karen A.; Auld, Grace; Sewell, Gavin; James, Sarah; Newson, Justine; Karra, Effie; Winstanley, Alison; Alazawi, William; Garcia-Marquez, Rita; Cordoba, Juan; Nicolaou, Anna; Gilroy, Derek W.
Patients with advanced cirrhosis experience frequent infections leading to sepsis, which carries high mortality. While innate immune dysfunction underlies this vulnerability, the precise cause remains elusive. We found prostaglandin (PGE2) elevated in acutely decompensated (AD) patients at immunosuppressive levels. Plasma from AD and end-stage liver disease (ESLD) patients suppressed macrophage cytokine secretion and bacteria killing in a PGE2 receptor-dependent manner, effects not seen in stable cirrhosis. Mouse models (bile duct ligation and CCL4-liver injury) also demonstrated elevated PGE2, which when inhibited completely restored immune competence and survival following infection. Importantly, albumin binds/inactivates PGE2 resulting in greater PGE2 bioavailability. This results in enhanced immunosuppressive effects of AD plasma in patients with low albumin levels. Administering albumin to AD patients reversed immunosuppressive properties of their plasma; protective effects recapitulated in rodent survival studies. Thus, elevated PGE2 combined with hypoalbuminemia mediates immunosuppression in AD and ESLD patients, which can be reversed with albumin. PMID:24728410
Lai, Xiao-ping; Yu, Xiao-jun; Qian, Hong; Wei, Lai; Lv, Jun-yao; Xu, Xiao-hu
Alcohol-related traumatic brain injury (TBI) is a common condition in medical and forensic practice, and results in high prehospital mortality. We investigated the mechanism of chronic alcoholism-related mortality by examining the effects of alcohol on the synapses of the medulla oblongata in a rat model of TBI. Seventy adult male Sprague-Dawley rats were randomly assigned to either ethanol (EtOH) group, EtOH-TBI group, or control groups (water group, water-TBI group). To establish chronic alcoholism model, rats in the EtOH group were given EtOH twice daily (4 g/kg for 2 weeks and 6 g/kg for another 2 weeks). The rats also received a minor strike on the occipital tuberosity with an iron pendulum. Histopathologic and ultrastructure changes and the numerical density of the synapses in the medulla oblongata were examined. Expression of postsynaptic density-95 (PSD-95) in the medulla oblongata was measured by ELISA. Compared with rats in the control group, rats in the chronic alcoholism group showed: (1) minor axonal degeneration; (2) a significant decrease in the numerical density of synapses (p < 0.01); and (3) compensatory increase in PSD-95 expression (p < 0.01). Rats in the EtOH-TBI group showed: (1) high mortality (50%, p < 0.01); (2) inhibited respiration before death; (3) severe axonal injury; and (4) decrease in PSD-95 expression (p < 0.05). Chronic alcoholism induces significant synapse loss and axonal impairment in the medulla oblongata and renders the brain more susceptible to TBI. The combined effects of chronic alcoholism and TBI induce significant synapse and axon impairment and result in high mortality.
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Jiang, Tianpeng; Wang, Lizhou; Li, Xing; Song, Jie; Wu, Xiaoping; Zhou, Shi
Long‑term and advanced cirrhosis is usually irreversible and often coincides with variceal hemorrhage or development of hepatocellular carcinoma; therefore, liver cirrhosis is a major cause of morbidity and mortality globally. The aim of the present study was to investigate the specific mechanism behind the formation of fibrosis or cirrhosis using rat models of hepatic fibrosis. The cirrhosis model was established by intraperitoneally administering dimethylnitrosamine to the rats. Hematoxylin and eosin staining was performed on the hepatic tissues of the rats to observe the fibrosis or cirrhosis, and western blot analysis was employed to detect α‑smooth muscle actin and desmin protein expression. Flow cytometric analysis was used to examine early and late apoptosis, and the protein and mRNA expression of endoplasmic reticulum (ER) stress-associated unfolded protein response (UPR) pathway proteins and apoptotic proteins [C/EBP homologous protein (CHOP) and caspase‑12] was detected by western blotting and the reverse-transcription polymerase chain reaction, respectively. The results indicated that the cirrhosis model was established successfully and that fibrosis was significantly increased in the cirrhosis model group compared with that in the normal control group. Flow cytometric analysis showed that early and late apoptosis in the cirrhosis model was significantly higher compared with that in the control group. The expression of the UPR pathway protein inositol-requiring enzyme (IRE) 1, as well as the expression of CHOP, was increased significantly in the cirrhotic rat tissues compared with that in the control group tissues (P<0.05). In conclusion, apoptosis was clearly observed in the hepatic tissue of cirrhotic rats, and the apoptosis was caused by activation of the ER stress-mediated IRE1 and CHOP.
Verma, Shashi Kant; Rastogil, Shweta; Arora, Indu; Javed, Kalim; Akhtar, Mohd; Samim, Mohd
Liver fibrosis is the common response to chronic liver injury and ultimately leads to cirrhosis. There is a pressing need in the pharmaceutical industry to develop efficient well-targeted drug delivery systems, which are lacking to date. This study was designed to investigate the efficacy of a nanoquercetin NQ; i.e., quercetin encapsulated in PAG (p-aminophenyl-1-thio-β-D-galactopryranoside)-coated NIPAAM (N-isopropyl acrylamide) nanopolymer in liver compared with naked quercetin (Q) using a carbon tetrachloride (CCl₄)-mediated liver cirrhosis model. NQ was more effective at restoring liver membrane integrity as indicated by significantly reduced serum markers, including Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH), compared with naked Q. The findings of reduced collagen and histopathology also show that the NQ effects were much better than those of naked Q. Biochemical parameters, including antioxidant defense enzymes, also provide supporting evidence. Furthermore, the decrease in NF-κB and NOS-2 expression in the NQ-treated groups was also much stronger than in the naked Q-treated group. Thus, the data clearly suggest that NQ not only provides significant hepatoprotection compared with naked Q, but it also substantially lowered the required concentration (1,000 to 10,000-fold lower) by increasing the bioavailability.
Plant, Martin, Ed.
Alcohol consumption has risen dramatically in many countries since the Second World War. Accompanying this rise has been a rise in alcohol-related problems, including liver cirrhosis mortality, alcohol dependence, and alcohol-related crimes and accidents. Alcohol misuse presents huge health, social, and legal problems throughout most of Europe and…
Kril, Jillian J.
Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions
Nishibe, Y; Kaneko, H; Suzuki, H; Abe, T; Matsuura, Y; Takaku, H
The wild-type baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects a range of mammalian cell types in vitro but does not replicate in these cells. The current study investigated the in vivo effect of AcMNPV in the mouse model of liver cirrhosis induced by the mutagen dimethylnitrosamine. Intraperitoneal injection of AcMNPV induced an immune response. The baculovirus was taken up by the liver and spleen where it suppressed liver injury and fibrosis through the induction of interferons. This study presents the first evidence of the feasibility of using baculovirus to treat liver cirrhosis.
Staples, Pamela A.
The study of older adults is relatively new for the social sciences. There is a growing awareness of the alcohol-related problems in this population. Between 2 and 10 percent of older social drinkers present severe alcohol-related problems of different kinds. Three terms describe the major consequences of "too much" alcohol: intoxication,…
The approach to treating alcohol-related problems in primary care settings needs: 1) to recognize the incidence of alcohol-related problems in primary care settings; 2) to know the way of screening; 3) to know how to help patients; and 4) to know enough about treating alcoholism to appropriately refer patients for additional help. This article looks research evidence about the incidence of alcohol-related problems in primary care and recognition of incidence and way of screening of alcohol-related problems by primary care physicians in Japan. Then this article describes evidence-based as well as author's experience-based approach to treat the alcohol-related health problems in primary care settings. In line with the newly introduced law to prevent the alcohol-related health problems and the anticipating introduction of new specialty of general medicine, early intervention to alcohol-related problems in primary care settings will be much appreciated. To do so, enough amounts of education and research are needed.
Lieber, C S
Alcohol affects the liver through metabolic disturbances associated with its oxidation. Redox changes produced by the hepatic alcohol dehydrogenase pathway affect lipid, carbohydrate and protein metabolism. Ethanol is also oxidized in liver microsomes by the ethanol-inducible cytochrome P4502E1, resulting in ethanol tolerance and selective hepatic perivenular damage. Furthermore, P4502E1 activates various xenobiotics, explaining the increased susceptibility of the heavy drinker to the toxicity of anesthetics, commonly used medications (i.e. isoniazid), analgesics (i.e. acetaminophen), and chemical carcinogens. Induction of microsomal enzymes also contributes to vitamin A depletion, enhances its hepatotoxicity and results in increased acetaldehyde generation from ethanol, with formation of protein adducts, glutathione depletion, free-radical-mediated toxicity, and lipid peroxidation. Chronic ethanol consumption strikingly enhances the number of hepatic collagen-producing activated lipocytes. Both in vivo (in our baboon model of alcoholic cirrhosis) and in vitro (in cultured myofibroblasts and activated lipocytes) ethanol and/or its metabolite acetaldehyde increase collagen accumulation and mRNA for collagen. Gender differences are related, in part, to lower gastric ADH activity (with consequent reduction of first pass ethanol metabolism) in young women, decreased hepatic fatty acid binding protein and increased free-fatty acid levels as well as lesser omega-hydroxylation, all of which result in increased vulnerability to ethanol. Elucidation of the biochemical effects of ethanol are now resulting in improved therapy: in baboons, S-adenosyl-L-methionine attenuates the ethanol-induced glutathione depletion and associated mitochondrial lesions, and polyenylphosphatidylcholine opposes the ethanol-induced hepatic phospholipid depletion, the decrease in phosphatidylethanolamine methyltransferase activity and the activation of hepatic lipocytes, with full prevention of
Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang
Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.
Morgan, M Y; Ross, M G; Ng, C M; Adams, D M; Thomas, H C; Sherlock, S
Ninety-two British, caucasian, alcoholic patients with liver disese were grouped on the basis of hepatic histology into fatty change, hepatitis with or without cirrhosis, and cirrhosis alone. Men with alcoholic hepatitis with or without cirrhosis showed an increased incidence of the histocompatibility antigen HLA-B8 (P less than 0.02). Increased measles antibody titres were found in patients without cirrhosis with or without hepatitis and were associated with the B8 phenotype in both sexes. Rubella antibody titres and percentage DNA-binding were raised in patients with cirrhosis and showed no association with the B8 phenotype. Concentrations of IgM and IgA were were raised in patients with stetosis and with hepatitis, while in patients with cirrhosis IgG concentrations were also increased. Low titres of autoantibodies were found in all histological groups. It is possible that the development of hepatitis in response to alcohol abuse may be influenced, at least in men, by a gene linked to the B locus. Otherwise, immune processes associated with alcohol-related liver disease are probably secondary phenomena. PMID:7400347
Zapater, Pedro; Gómez-Hurtado, Isabel; Peiró, Gloria; González-Navajas, José Manuel; García, Irma; Giménez, Paula; Moratalla, Alba; Such, José; Francés, Rubén
Background Bacterial translocation is a frequent event in cirrhosis leading to an increased inflammatory response. Splanchnic adrenergic system hyperactivation has been related with increased bacterial translocation. We aim at evaluating the interacting mechanism between hepatic norepinephrine and inflammation during liver damage in the presence of bacterial-DNA. Animals and Methods Forty-six mice were included in a 16-week protocol of CCl4-induced cirrhosis. Laparotomies were performed at weeks 6, 10, 13 and 16. A second set of forty mice injected with a single intraperitoneal dose of CCl4 was treated with saline, 6-hydroxidopamine, Nebivolol or Butoxamine. After 5 days, mice received E. coli-DNA intraperitoneally. Laparotomies were performed 24 hours later. Liver bacterial-DNA, norepinephrine, TNF-alpha, IL-6 and beta-adrenergic receptor levels were measured. Results Bacterial-DNA translocation was more frequent in CCl4-treated animals compared with controls, and increased as fibrosis progressed. Liver norepinephrine and pro-inflammatory cytokines were significantly higher in mice with vs without bacterial-DNA (319.7±120.6 vs 120.7±68.6 pg/g for norepinephrine, 38.4±6.1 vs 29.7±4.2 pg/g for TNF-alpha, 41.8±7.4 vs 28.7±4.3 pg/g for IL-6). Only beta-adrenergic receptor-1 was significantly increased in treated vs control animals (34.6±7.3 vs 12.5±5.3, p = 0.01) and correlated with TNF-alpha, IL-6 and norepinephrine hepatic levels in animals with bacterial-DNA. In the second set of mice, cytokine levels were increased in 6-hydroxidopamine and Nebivolol (beta-adrenergic receptor-1 antagonist) treated mice compared with saline. Butoxamine (beta-adrenergic receptor-2 antagonist) didn’t inhibit liver norepinephrine modulation of pro-inflammatory cytokines. Conclusions Beta-adrenergic receptor-1 mediates liver norepinephrine modulation of the pro-inflammatory response in CCl4-treated mice with bacterial-DNA. PMID:22916250
Mackenbach, Johan P.; Kulhánová, Ivana; Bopp, Matthias; Borrell, Carme; Deboosere, Patrick; Kovács, Katalin; Looman, Caspar W. N.; Leinsalu, Mall; Mäkelä, Pia; Martikainen, Pekka; Menvielle, Gwenn; Rodríguez-Sanz, Maica; Rychtaříková, Jitka; de Gelder, Rianne
Background Socioeconomic inequalities in alcohol-related mortality have been documented in several European countries, but it is unknown whether the magnitude of these inequalities differs between countries and whether these inequalities increase or decrease over time. Methods and Findings We collected and harmonized data on mortality from four alcohol-related causes (alcoholic psychosis, dependence, and abuse; alcoholic cardiomyopathy; alcoholic liver cirrhosis; and accidental poisoning by alcohol) by age, sex, education level, and occupational class in 20 European populations from 17 different countries, both for a recent period and for previous points in time, using data from mortality registers. Mortality was age-standardized using the European Standard Population, and measures for both relative and absolute inequality between low and high socioeconomic groups (as measured by educational level and occupational class) were calculated. Rates of alcohol-related mortality are higher in lower educational and occupational groups in all countries. Both relative and absolute inequalities are largest in Eastern Europe, and Finland and Denmark also have very large absolute inequalities in alcohol-related mortality. For example, for educational inequality among Finnish men, the relative index of inequality is 3.6 (95% CI 3.3–4.0) and the slope index of inequality is 112.5 (95% CI 106.2–118.8) deaths per 100,000 person-years. Over time, the relative inequality in alcohol-related mortality has increased in many countries, but the main change is a strong rise of absolute inequality in several countries in Eastern Europe (Hungary, Lithuania, Estonia) and Northern Europe (Finland, Denmark) because of a rapid rise in alcohol-related mortality in lower socioeconomic groups. In some of these countries, alcohol-related causes now account for 10% or more of the socioeconomic inequality in total mortality. Because our study relies on routinely collected underlying causes of
DiBello, Angelo M; Rodriguez, Lindsey M; Hadden, Benjamin W; Neighbors, Clayton
Previous research suggests that both jealousy and relationship contingent self-esteem (RCSE) are related to alcohol use and alcohol-related problems. No work, however, has examined these two constructs together as they relate to motives for alcohol use and alcohol-related problems. The current study aims to build upon emerging literature examining different types of jealousy (i.e., emotional, cognitive, and behavioral), relationship quality (i.e., satisfaction, commitment, closeness), RCSE, and alcohol use. More specifically, the current study aimed to examine the associations between RCSE and drinking to cope and RCSE and alcohol-related problems, in the context of the different types of jealousy. Moreover, the current study aimed to assess whether the associations between RCSE, jealousy, and drinking outcomes vary as a function of relationship quality. Two hundred and seventy seven individuals (87% female) at a large southern university participated in the study. They completed measures of RCSE, relationship satisfaction, commitment, closeness, and jealousy as well as alcohol-related outcomes. Using PROCESS, moderated mediational analyses were used to evaluate different types of jealousy as mediators of the association between RCSE and drinking to cope/alcohol-related problems. Further, we aimed to examine whether relationship quality moderated the association between RCSE and jealousy in predicting alcohol-related variables. Results indicated that cognitive jealousy mediated the association between both RCSE and drinking to cope and RCSE and alcohol-related problems. Further, relationship satisfaction, commitment, and closeness were all found to moderate the association between RSCE and cognitive jealousy such that at lower, but not higher levels of satisfaction, commitment, and closeness, cognitive jealousy mediated the association between RCSE and drinking to cope and RCSE and alcohol-related problems.
Tripp, Jessica C.; McDevitt-Murphy, Meghan E.; Avery, Megan L.; Bracken, Katherine L.
Objective Posttraumatic stress disorder (PTSD), alcohol use, and alcohol-related consequences have been linked to emotion dysregulation. Sex differences exist in both emotion regulation dimensions and alcohol use patterns. This investigation examined facets of emotion dysregulation as potential mediators of the relationship between PTSD symptoms and alcohol-related consequences and whether differences may exist across sexes. Methods Participants included 240 college students with a trauma history who reported using alcohol within the past three months and completed measures of PTSD symptoms, emotion dysregulation, alcohol consumption, alcohol-related consequences, and negative affect. The six facets of emotion dysregulation were examined as mediators of the relationship between PTSD symptoms and alcohol-related consequences in the full sample and by sex. Results There were differences in sexes on several variables, with women reporting higher PTSD scores and Lack of Emotional Awareness. Men reported significantly higher drinks per week in a typical week and a heavy week. There were significant associations between the variables for the full sample, with PTSD showing associations with five facets of emotion dysregulation subscales: Impulse Control Difficulties when Upset, Difficulties Engaging in Goal-Directed Behavior, Nonacceptance of Emotional Responses, Lack of Emotional Clarity, and Limited Access to Emotion Regulation Strategies. Alcohol-related consequences were associated with four aspects of emotion dysregulation: Impulse Control Difficulties when Upset, Difficulties Engaging in Goal-Direct Behavior, Nonacceptance of Emotional Reponses, and Limited Access to Emotion Regulation Strategies. Two aspects of emotion regulation, Impulse Control Difficulties and Difficulties Engaging in Goal Directed Behavior, mediated the relationship between PTSD symptoms and alcohol-related consequences in the full sample, even after adjusting for the effects of negative affect
Godlaski, Aaron J; Giancola, Peter R
The purpose of this investigation was to examine (a) whether irritability mediates the relation between executive functioning (EF) and alcohol-related aggression and (b) whether the alcohol-aggression relation is better explained by the interactive effects of EF and irritability above and beyond the effects of either variable alone. EF was measured using seven well-established neuropsychological tests. Irritability was assessed with the Caprara Irritability Scale. Participants were 313 male and female social drinkers between 21 and 35 years of age. Following the consumption of an alcohol or a placebo beverage, participants were tested on a laboratory aggression task in which electric shocks were given to and received from a fictitious opponent under the guise of a competitive reaction-time task. Aggression was operationalized as the shock intensities administered to the fictitious opponent. Results indicated that irritability successfully mediated the relation between EF and intoxicated aggression for men only. Despite the fact that irritability and EF both independently moderated the alcohol-aggression relation in previous studies, no significant interaction for their combined effect was detected here. The findings are discussed, in part, within a cognitive neoassociationistic framework for aggressive behavior.
... 49 Transportation 5 2014-10-01 2014-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...
... 49 Transportation 7 2013-10-01 2013-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...
... 49 Transportation 7 2014-10-01 2014-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...
... 49 Transportation 5 2011-10-01 2011-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...
... 49 Transportation 3 2010-10-01 2010-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...
... 49 Transportation 5 2010-10-01 2010-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...
... 49 Transportation 7 2011-10-01 2011-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...
... 49 Transportation 5 2012-10-01 2012-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...
... 49 Transportation 7 2010-10-01 2010-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...
... 49 Transportation 3 2011-10-01 2011-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...
... 49 Transportation 3 2013-10-01 2013-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...
... 49 Transportation 5 2013-10-01 2013-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...
... 49 Transportation 3 2014-10-01 2014-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...
... 49 Transportation 7 2012-10-01 2012-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...
... 49 Transportation 3 2012-10-01 2012-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...
... medlineplus.gov/ency/article/000282.htm Primary biliary cirrhosis To use the sharing features on this page, ... and leads to scarring of the liver called cirrhosis. This is called biliary cirrhosis. Causes The cause ...
Voas, Robert B.; Fell, James C.
Alcohol-related health policy research is responsible for guiding the implementation of laws and public health policies that have reduced alcohol-related highway injuries and deaths, as well as other alcohol-related problems over the last 40 years. This research, which tests theories about potential policy changes and responds to specific problems, has examined a vast array of prevention programs. This article briefly identifies 10 program categories and highlights four programs to illustrate the scope and complexity of the individual health policy areas within the categories. PMID:23579933
Ferns, Terry; Cork, Alison
Internationally, violence in the emergency department (ED) is of a constant concern to emergency practitioners. Frequently, both original research papers and anecdotal reports emphasise the phenomenon of alcohol related aggression in the ED. In this first paper, we highlight the literatures discussion of alcohol related violence in the emergency department and the potential psychological effects of alcohol intoxication. In the second we offer personal and organisational strategies clinical nursing staff may consider appropriate to minimise the risk of assault when caring for service users projecting alcohol related aggression.
Orchowski, Lindsay M; Mastroleo, Nadine R; Borsari, Brian
The prevalence of alcohol-related regretted sex in college students warrants a better understanding of the characteristics of students who report such experiences. Therefore, the present study examined correlates of regretted sexual experiences involving alcohol use among 2 specific high-risk college student samples: students mandated to alcohol intervention (n = 522) and volunteer 1st-year students transitioning to college (n = 481). Results indicated that alcohol-related regretted sex occurred at similar rates in mandated and volunteer students, with approximately 25% of the students reporting at least 1 occurrence in the past month. Women were more likely to report alcohol-related regretted sex compared with men. The belief that alcohol use would result in "liquid courage" was associated with alcohol-related regretted sex among college students, even after accounting for greater alcohol use and problem alcohol use behaviors. These findings have significant implications for intervention efforts and future research.
Orchowski, Lindsay M.; Mastroleo, Nadine R.; Borsari, Brian
The prevalence of alcohol-related regretted sex in college students warrants a better understanding of the characteristics of students who report such experiences. Therefore, the present study examined correlates of regretted sexual experiences involving alcohol use among two specific high-risk college student samples: Students mandated to alcohol intervention (N = 522) and volunteer first-year students transitioning to college (N = 481). Results indicated that alcohol-related regretted sex occurred in similar rates in mandated and volunteer students, with approximately 25% of the students reporting at least one occurrence in the past month. Women were more likely to report alcohol-related regretted sex compared to men. The belief that alcohol use would result in “liquid courage” was associated with alcohol-related regretted sex among college students, even after accounting for greater alcohol use and problem alcohol use behaviors. These findings have significant implications for intervention efforts and future research. PMID:22448762
Arterberry, Brooke J; Smith, Ashley E; Martens, Matthew P; Cadigan, Jennifer M; Murphy, James G
The present study examined the unique contributions of protective behavioral strategies and social norms in predicting alcohol-related outcomes. Participants were 363 students from a large public university in the Midwest who reported at least one binge-drinking episode (5+/4+ drinks for men/women in one sitting) in the past 30 days. Data were collected 1/2010-3/2011. We used SEM to test models where protective behavioral strategies (PBS) and social norms were predictors of both alcohol use and alcohol-related problems, after controlling for the effects of gender. Both PBS and descriptive norms had relationships with alcohol use. PBS also had a relationship with alcohol-related problems. Overall, the findings suggest that PBS and social norms have unique associations with distinct alcohol-related outcomes.
REDUCING ALCOHOL-RELATED SEXUAL ASSAULT IN THE MARINE CORPS 5a.&CONTRACT&NUMBER! N/A 5b.&GRANT&NUMBER! N/A 5c.&PROGRAM&ELEMENT&NUMBER! N/A 6...reduce alcohol-related sexual assault in the Marine Corps. It advocates more emphasis and training on the interplay between alcohol and sexual ...assault, as well as male and female-specific training on the issue. 15.&SUBJECT&TERMS! Sexual Assault, Alcohol, Incapacitation, Marine Corps
Cork, Alison; Ferns, Terry
Violence in the emergency department (ED) is a global problem. In our first paper, we highlighted the potential psychological effects of alcohol intoxication, the literatures discussion of alcohol related violence in the emergency department and the importance of developing positive nurse/service user relationships. In this second paper, we discuss personal and organisational strategies clinical nursing staff may consider appropriate to minimise the risk of assault when caring for service users projecting alcohol related aggression.
Brown, Stephen L; Coyne, Sarah M; Barlow, Alexandra; Qualter, Pamela
In adults, alcohol-related stimuli prime aggressive responding without ingestion or belief of ingestion. This represents either experiential or socially-and culturally-mediated learning. Using a laboratory-based competitive aggression paradigm, we replicated adult findings in 103 11-14 year old adolescents below the legal UK drinking age. Using a two-independent group design, priming with alcohol-related imagery led participants to deliver louder noise punishments in a competition task than priming with beverage-related images. This effect was stronger in participants scoring low on an internalization measure. Priming effects in relatively alcohol-naïve participants could constitute evidence of socio-cultural transmission of scripts linking alcohol use and aggression. The enhanced effect in lower internalization scorers suggests that alcohol priming might undermine behavioral inhibition processes in otherwise stable adolescents.
Pearson, Matthew R.; Kite, Benjamin A.; Henson, James M.
In the present study, we examined whether the use of protective behavioral strategies (PBS) mediates the effects of impulsivity-like traits on alcohol-related problems using a sample of 278 college students. Validating the 5-factor model of impulsivity, we showed that each impulsivity-like trait had a distinct pattern of relationships with PBS…
Lambe, Laura; Mackinnon, Sean P; Stewart, Sherry H
The motivational model of alcohol use posits that individuals may consume alcohol to cope with negative affect. Conflict with others is a strong predictor of coping motives, which in turn predict alcohol-related problems. Two studies examined links between conflict, coping motives, and alcohol-related problems in emerging adult romantic dyads. It was hypothesized that the association between conflict and alcohol-related problems would be mediated by coping-depression and coping-anxiety motives. It was also hypothesized that this would be true for actor (i.e., how individual factors influence individual behaviors) and partner effects (i.e., how partner factors influence individual behaviors) and at the between- (i.e., does not vary over the study period) and within-subjects (i.e., varies over the study period) levels. Both studies examined participants currently in a romantic relationship who consumed ≥12 alcoholic drinks in the past year. Study 1 was cross-sectional using university students (N = 130 students; 86.9% female; M = 21.02 years old, SD = 3.43). Study 2 used a 4-wave, 4-week longitudinal design with romantic dyads (N = 100 dyads; 89% heterosexual; M = 22.13 years old, SD = 5.67). In Study 2, coping-depression motives emerged as the strongest mediator of the conflict-alcohol-related problems association, and findings held for actor effects but not partner effects. Supplemental analyses revealed that this mediational pathway only held among women. Within any given week, alcohol-related problems changed systematically in the same direction between romantic partners. Interventions may wish to target coping-depression drinking motives within couples in response to conflict to reduce alcohol-related problems.
Zhang, Hang; Wu, Lian-Ying; Zhang, Shuai; Qiu, Li-Yan; Li, Nan; Zhang, Xuan; Zhang, Xue-Zhi; Shan, Chang-Liang; Ye, Li-Hong; Zhang, Xiao-Dong
Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma (HCC). However, the significance of circulating antibody to hepatitis B virus X antigen (anti-HBx) in sera remains unclear. In the present study, we examined the titers of anti-HBx (IgG) in the sera from 173 patients with chronic hepatitis B (CHB), 106 liver cirrhosis (LC), and 61 HCC by enzyme-linked immunosorbent assay (ELISA), respectively. Our data showed that the positive rates of anti-HBx were higher in sera of LC (40.6%) and HCC (34.4%) than those of CHB (10.4%), P < .05. In all 40 patients with anti-HBx+ out of 340 patients, 39 (97.5%) were HBsAg/HBeAg/anti-HBc+ and 1 (2.5%) was anti-HBs+ (P < .01), suggesting that anti-HBx in sera is a marker of HBV replication rather than a protective antibody. Thus, our findings reveal that circulating anti-HBx in sera is one of the markers of development of LC and HCC mediated by HBV.
Klein, Hugh; Shiffman, Kenneth S
This study, based on a stratified (by decade of production) random sample of 1,221 animated cartoons and 4,201 characters appearing in those cartoons, seeks to determine the prevalence of alcohol-related content; how, if at all, the prevalence changed between 1930 and 1996 (the years spanned by this research); and the types of messages that animated cartoons convey about beverage alcohol and drinking in terms of the characteristics that are associated with alcohol use, the contexts in which alcohol is used in cartoons, and the reasons why cartoon characters purportedly consume alcohol. Approximately 1 cartoon in 11 was found to contain alcohol-related content, indicating that the average child or adolescent viewer is exposed to approximately 24 alcohol-related messages each week just from the cartoons that he/she watches. Data indicated that the prevalence of alcohol-related content declined significantly over the years. Quite often, alcohol consumption was shown to result in no effects whatsoever for the drinker, and alcohol use often occurred when characters were alone. Overall, mixed, ambivalent messages were provided about drinking and the types of characters that did/not consume alcoholic beverages.
Brown, James D.
Since the first publication on fetal alcohol syndrome appeared in the scientific literature over 30 years ago, there has been a great deal of research interest in the topic. This paper reviews findings within the past 10 years related to causes, frequency, and diagnosis of alcohol-related disabilities, before turning to the impact these…
Klein, Hugh; Shiffman, Kenneth S.
This study, based on a stratified (by decade of production) random sample of 1,221 animated cartoons and 4,201 characters appearing in those cartoons, seeks to determine the prevalence of alcohol-related content; how, if at all, the prevalence changed between 1930 and 1996 (the years spanned by this research); and the types of messages that animated cartoons convey about beverage alcohol and drinking in terms of the characteristics that are associated with alcohol use, the contexts in which alcohol is used in cartoons, and the reasons why cartoon characters purportedly consume alcohol. Approximately 1 cartoon in 11 was found to contain alcohol-related content, indicating that the average child or adolescent viewer is exposed to approximately 24 alcohol-related messages each week just from the cartoons that he/she watches. Data indicated that the prevalence of alcohol-related content declined significantly over the years. Quite often, alcohol consumption was shown to result in no effects whatsoever for the drinker, and alcohol use often occurred when characters were alone. Overall, mixed, ambivalent messages were provided about drinking and the types of characters that did/not consume alcoholic beverages. PMID:24350176
Hoffman, Eric W.; Pinkleton, Bruce E.; Weintraub Austin, Erica; Reyes-Velázquez, Wanda
Objective: Alcohol marketers have increasingly moved their advertising efforts into digital and social media venues. As a result, the purpose of this study is to investigate associations between students' use of social media, their exposure to alcohol marketing messages through social media, and their alcohol-related beliefs and behaviors.…
Mallett, Kimberly A.; Turrisi, Rob; Cleveland, Michael J.; Scaglione, Nichole M.; Reavy, Racheal; Sell, Nichole M.; Varvil-Weld, Lindsey
Objective: Despite showing reductions in college student drinking, interventions have shown some inconsistency in their ability to successfully decrease consequences. With the goal of improving prevention efforts, the purpose of this study was to examine the role of consequence-specific constructs, in addition to drinking, that influence students’ experiences with alcohol-related problems. The study examined how drinking and protective behaviors mediated the relationships between students’ willingness to experience consequences, intentions to avoid them, and four categories of alcohol-related problems (physiological, social, sexual, and academic). Method: First-year college student drinkers (n = 2,024) at a large northeastern university completed surveys during the fall and spring of their freshman year. Results: As expected, different patterns of associations emerged for physiological and nonphysiological consequences. When physiological consequences (e.g., hangover, vomiting) were examined, drinking significantly mediated the effect of willingness on the consequences. Drinking-specific protective behaviors indirectly influenced consequences through drinking behaviors whereas general protective behaviors did not. When nonphysiological (e.g., social, sexual, academic) consequences were examined, drinking and general protective behaviors emerged as significant mediators of the effects of willingness and intentions on the consequences, whereas drinking-specific protective behaviors did not. Conclusions: The results suggest that prevention efforts (e.g., personalized feedback) could be tailored to address specific types of protective behaviors as well as specific types of consequences frequently experienced by college students. PMID:26562594
Wilkins, Benjamin J.; Lorent, Kristin; Matthews, Randolph P.; Pack, Michael
North American Indian Childhood Cirrhosis (NAIC) is a rare, autosomal recessive, progressive cholestatic disease of infancy affecting the Cree-Ojibway first Nations of Quebec. All NAIC patients are homozygous for a missense mutation (R565W) in CIRH1A, the human homolog of the yeast nucleolar protein Utp4. Utp4 is part of the t-Utp subcomplex of the small subunit (SSU) processome, a ribonucleoprotein complex required for ribosomal RNA processing and small subunit assembly. NAIC has thus been proposed to be a primary ribosomal disorder (ribosomopathy); however, investigation of the pathophysiologic mechanism of this disease has been hindered by lack of an animal model. Here, using a morpholino oligonucleotide (MO)-based loss-of-function strategy, we have generated a model of NAIC in the zebrafish, Danio rerio. Zebrafish Cirhin shows substantial homology to the human homolog, and cirh1a mRNA is expressed in developing hepatocytes and biliary epithelial cells. Injection of two independent MOs directed against cirh1a at the one-cell stage causes defects in canalicular and biliary morphology in 5 dpf larvae. In addition, 5 dpf Cirhin-deficient larvae have dose-dependent defects in hepatobiliary function, as assayed by the metabolism of an ingested fluorescent lipid reporter. Previous yeast and in vitro studies have shown that defects in ribosome biogenesis cause stabilization and nuclear accumulation of p53, which in turn causes p53-mediated cell cycle arrest and/or apoptosis. Thus, the nucleolus appears to function as a cellular stress sensor in some cell types. In accordance with this hypothesis, transcriptional targets of p53 are upregulated in Cirhin-deficient zebrafish embryos, and defects in biliary function seen in Cirhin-deficient larvae are completely abrogated by mutation of tp53. Our data provide the first in vivo evidence of a role for Cirhin in biliary development, and support the hypothesis that congenital defects affecting ribosome biogenesis can activate
Simons, Jeffrey S; Christopher, Michael S; McLaury, Ann E
This study examined relations between personal strivings and alcohol use among college students. Personal strivings are ongoing goals that individuals are characteristically trying to achieve through their behavior. Participants generated lists of personal strivings following standard instructions and then completed an assessment of alcohol use and related problems. Participants returned to complete a follow-up assessment of drinking behavior after 30 days. Personal strivings were coded into content categories by trained raters using a coding manual. Four content categories were examined for this study: achievement, affiliation, health, and self-presentation. A series of t tests revealed that participants endorsing achievement strivings reported less alcohol-related problems and marginally fewer instances of binge drinking during the 30-day follow-up period. In contrast, participants endorsing self-presentation strivings reported more alcohol-related problems during the follow-up period.
Tourism and fatal single motor vehicle accidents, an index of alcohol-related motor accidents, are examined in a cross-sectional analysis of the 50 states of the Union and the District of Columbia. A multiple regression model is employed in which average mileage driven, percent of metropolitan residents, and number of licensed drivers are statistically controlled. Tourism is found to be positively associated with the single motor vehicle fatality rate. Further research and policy implications are discussed.
Nguyen, Van Anh; Le, Tran; Tong, Ming; Mellion, Michelle; Gilchrist, James; de la Monte, Suzanne M.
The mechanisms of alcohol-related peripheral neuropathy (ALPN) are poorly understood. We hypothesize that, like alcohol-related liver and brain degeneration, ALPN may be mediated by combined effects of insulin/IGF resistance and oxidative stress. Adult male Long Evans rats were chronically pair-fed with diets containing 0% or 37% ethanol (caloric), and subjected to nerve conduction studies. Chronic ethanol feeding slowed nerve conduction in the tibial (p = 0.0021) motor nerve, and not plantar sensory nerve, but it did not affect amplitude. Histological studies of the sciatic nerve revealed reduced nerve fiber diameters with increased regenerative sprouts, and denervation myopathy in ethanol-fed rats. qRT-PCR analysis demonstrated reduced mRNA levels of insulin, IGF-1, and IGF-2 polypeptides, IGF-1 receptor, and IRS2, and ELISAs revealed reduced immunoreactivity for insulin and IGF-1 receptors, IRS-1, IRS-4, myelin-associated glycoprotein, and tau in sciatic nerves of ethanol-fed rats (all p < 0.05 or better). The findings suggest that ALPN is characterized by (1) slowed conduction velocity with demyelination, and a small component of axonal degeneration; (2) impaired trophic factor signaling due to insulin and IGF resistance; and (3) degeneration of myelin and axonal cytoskeletal proteins. Therefore, ALPN is likely mediated by molecular and signal transduction abnormalities similar to those identified in alcoholic liver and brain degeneration. PMID:23016131
Buyse, S; Durand, F; Joly, F
The liver plays a key role in the metabolism of nutrients. Therefore, liver failure is often associated with malnutrition. It is well-established that malnutrition is an independent prognostic factor in patients with cirrhosis and liver failure. Since standard anthropometric and biological indexes are associated with liver dysfunction, nutritional assessment is difficult in patients with cirrhosis. In this review, we explain the various causes and mechanisms leading to malnutrition in cirrhosis. We also describe reliable methods used to assess the nutritional condition of these patients. Finally, we stress the importance of nutritional care in cirrhosis and liver dysfunction, describing its specific characteristics and indications.
Bullying perpetration and victimization as externalizing and internalizing pathways: A retrospective study linking parenting styles and self-esteem to depression, alcohol use, and alcohol-related problems
Patock-Peckham, Julie A; Medina, Mia; Terrell, Nathan; Belton, Daniel; King, Kevin M
Emerging research suggests significant positive associations between bullying and substance use behaviors. However, these studies typically focused either on the link between substance use and bullying perpetration or victimization, and few have conceptualized bullying perpetration and/or victimization as mediators. In this study, we simultaneously tested past bullying perpetration and victimization as mediational pathways from retrospective report of parenting styles and global self-esteem to current depressive symptoms, alcohol use and alcohol-related problems. Data were collected from a college sample of 419 drinkers. Mediation effects were conducted using a bias-corrected bootstrap technique in structural equation modeling. Two-path mediation analyses indicated that mother and father authoritativeness were protective against bully victimization and depression through higher self-esteem. Conversely, having a permissive or authoritarian mother was positively linked to bullying perpetration, which in turn was associated with increased alcohol use, and to a lesser degree, more alcohol-related problems. Mother authoritarianism was associated with alcohol-related problems through depressive symptoms. Three-path mediation analyses suggested a trend in which individuals with higher self-esteem were less likely to report alcohol-related problems through lower levels of bullying victimization and depression. Results suggested that bullying perpetration and victimization may respectively serve as externalizing and internalizing pathways through which parenting styles and self-esteem are linked to depression and alcohol-related outcomes. The present study identified multiple modifiable precursors of, and mediational pathways to, alcohol-related problems which could guide the development and implementation of prevention programs targeting problematic alcohol use. PMID:26757486
Litt, Dana M; Stock, Michelle L
The present study examined the impact of socially based descriptive norms on willingness to drink alcohol, drinker prototype favorability, affective alcohol attitudes, and perceived vulnerability for alcohol-related consequences within the Prototype Willingness model. Descriptive norms were manipulated by having 189 young adolescents view experimenter-created profile pages from the social networking site Facebook, which either showed older peers drinking or not. The results provided evidence that descriptive norms for alcohol use, as portrayed by Facebook profiles, significantly impact willingness to use, prototypes, attitudes toward use, and perceived vulnerability. A multiple mediation analysis indicated that prototypes, attitudes, and perceptions of use mediated the relationship between the content of the Facebook profile and willingness. These results indicate that adolescents who perceive that alcohol use is normative, as evidenced by Facebook profiles, are at higher risk for cognitions shown to predict alcohol use than adolescents who do not see alcohol use portrayed as frequently on Facebook.
Martínez-Esparza, María; Tristán-Manzano, María; Ruiz-Alcaraz, Antonio J; García-Peñarrubia, Pilar
This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to
Carey, Elizabeth J; Ali, Ahmad H; Lindor, Keith D
Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduöction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options.
Buckner, Julia D; Matthews, Russell A
Individuals with elevated social anxiety appear particularly vulnerable to experiencing alcohol-related problems; yet we know little about factors that may account for this relationship. One possibility is that socially anxious individuals hold beliefs about the impressions they make on others while drinking and these beliefs play an important role in their drinking behaviors. The present study used exploratory factor analysis among participants with clinically elevated social anxiety (n=166) to develop a measure, the Social Impressions while Drinking Scale (SIDS), to assess beliefs regarding others' impressions of drinking behaviors that may be particularly relevant to socially anxious individuals. A valuations scale was also developed to assess the importance of each belief. Empirically-derived subscales were identified with adequate reliability. Among socially anxious participants, the Gregarious and Sexual Facilitation subscales were uniquely related to drinking problems and frequency respectively. Individuals with clinically meaningful social anxiety achieved higher scores on all SIDS subscales compared to those with lower social anxiety (n=166). Several SIDS scales mediated the relations between social anxiety group status and drinking problems (Interaction Fears, Observation Fears, Aggression, Gregariousness). Results highlight the importance of examining beliefs specific to high-risk populations in assessing their alcohol-related behaviors.
Beck, Anne; Heinz, Adrienne J; Heinz, Andreas
Alcohol-related violence, a longstanding, serious, and pervasive social problem, has provided researchers from diverse disciplines with a model to study individual differences in aggressive and violent behavior. Of course, not all alcohol consumers will become aggressive after drinking and similarly, not all individuals with alcohol use disorders will exhibit such untoward behavior. Rather, the relationship is best conceptualized as complex and indirect and is influenced by a constellation of social, cognitive, and biological factors that differ greatly from one person to the next. Animal experiments and human studies have elucidated how these mechanisms and processes explain (i.e., mediate) the relation between acute and chronic alcohol consumption and aggressive behavior. Further, the rich body of literature on alcohol-related aggression has allowed for identification of several potential high-yield targets for clinical intervention, e.g., cognitive training for executive dysfunction; psychopharmacology targeting affect and threat perception, which may also generalize to other psychiatric conditions characterized by aggressive behavior. Here we aim to integrate pertinent findings, derived from different methodological approaches and theoretical models, which explain heterogeneity in aggressive responses to alcohol. A translational platform is provided, highlighting common factors linking alcohol and aggression that warrant further, interdisciplinary study in order to reduce the devastating social impact of this phenomenon.
Zahr, Natalie M; Kaufman, Kimberley L; Harper, Clive G
One of the sequelae of chronic alcohol abuse is malnutrition. Importantly, a deficiency in thiamine (vitamin B(1)) can result in the acute, potentially reversible neurological disorder Wernicke encephalopathy (WE). When WE is recognized, thiamine treatment can elicit a rapid clinical recovery. If WE is left untreated, however, patients can develop Korsakoff syndrome (KS), a severe neurological disorder characterized by anterograde amnesia. Alcohol-related brain damage (ARBD) describes the effects of chronic alcohol consumption on human brain structure and function in the absence of more discrete and well-characterized neurological concomitants of alcoholism such as WE and KS. Through knowledge of both the well-described changes in brain structure and function that are evident in alcohol-related disorders such as WE and KS and the clinical outcomes associated with these changes, researchers have begun to gain a better understanding of ARBD. This Review examines ARBD from the perspective of WE and KS, exploring the clinical presentations, postmortem brain pathology, in vivo MRI findings and potential molecular mechanisms associated with these conditions. An awareness of the consequences of chronic alcohol consumption on human behavior and brain structure can enable clinicians to improve detection and treatment of ARBD.
Li, R; Barton, HA; Maurer, TS
Liver cirrhosis is a disease characterized by the loss of functional liver mass. Physiologically based pharmacokinetic (PBPK) modeling was applied to interpret and predict how the interplay among physiological changes in cirrhosis affects pharmacokinetics. However, previous PBPK models under cirrhotic conditions were developed for permeable cytochrome P450 substrates and do not directly apply to substrates of liver transporters. This study characterizes a PBPK model for liver transporter substrates in relation to the severity of liver cirrhosis. A published PBPK model structure for liver transporter substrates under healthy conditions and the physiological changes for cirrhosis are combined to simulate pharmacokinetics of liver transporter substrates in patients with mild and moderate cirrhosis. The simulated pharmacokinetics under liver cirrhosis reasonably approximate observations. This analysis includes meta-analysis to obtain system-dependent parameters in cirrhosis patients and a top-down approach to improve understanding of the effect of cirrhosis on transporter-mediated drug disposition under cirrhotic conditions. PMID:26225262
MELLION, MICHELLE L.; NGUYEN, VANANH; TONG, MING; GILCHRIST, JAMES; DE LA MONTE, SUZANNE
Introduction The aim of this work was to determine the effect of chronic alcohol exposure on peripheral nerves in a nutritionally balanced rat model of alcoholism. Methods Three different strains of adult male rats were pair-fed for 8 weeks with isocaloric liquid diets containing 0% or 37% ethanol. Nerve conduction studies (NCS) were performed. Peripheral nerve and muscle were examined histologically with morphometrics. Results Ethanol exposure significantly slowed velocity in tibial and fibular nerves, but not in the plantar nerve in all 3 strains. Studies of the sciatic nerve revealed decreased fiber diameters and increased regenerative sprouts in peripheral nerves. There was muscle denervation of ethanol-exposed rats in all 3 strains. Conclusions Chronic ethanol exposure caused a polyneuropathy characterized by axonal degeneration despite adequate nutrition. These results suggest that ethanol exposure has direct neurotoxic effects on peripheral nerves. This model may be useful in understanding the underlying mechanism(s) of alcohol-related peripheral neuropathy. PMID:23761140
Heinz, Adrienne J; Beck, Anne; Meyer-Lindenberg, Andreas; Sterzer, Philipp; Heinz, Andreas
Alcohol-related violence is a serious and common social problem. Moreover, violent behaviour is much more common in alcohol-dependent individuals. Animal experiments and human studies have provided insights into the acute effect of alcohol on aggressive behaviour and into common factors underlying acute and chronic alcohol intake and aggression. These studies have shown that environmental factors, such as early-life stress, interact with genetic variations in serotonin-related genes that affect serotonergic and GABAergic neurotransmission. This leads to increased amygdala activity and impaired prefrontal function that, together, predispose to both increased alcohol intake and impulsive aggression. In addition, acute and chronic alcohol intake can further impair executive control and thereby facilitate aggressive behaviour.
Goh, George Boon-Bee; Chow, Wan-Cheng; Renwei-Wang; Yuan, Jian-Min; Koh, Woon-Puay
Limited experimental and epidemiologic data suggest that coffee may reduce hepatic damage in chronic liver disease. The association between consumption of coffee and other beverages, and risk of cirrhosis mortality was evaluated in The Singapore Chinese Health Study. This is a prospective population-based cohort of 63,275 middle-aged and older Chinese subjects who provided data on diet, lifestyle and medical histories through in-person interviews using structured questionnaire at enrollment between 1993 and 1998. Mortality from cirrhosis in the cohort was ascertained through linkage analysis with nationwide death registry. After a mean follow-up of 14.7 years, 114 subjects died from cirrhosis; 33 of them from viral hepatitis B (29%), two from hepatitis C (2%), and 14 from alcohol-related cirrhosis (12%). Compared to non-drinkers, daily alcohol drinkers had a strong dose-dependent positive association between amount of alcohol and risk of cirrhosis mortality. Conversely, there was a strong dose-dependent inverse association between coffee intake and risk of non-viral hepatitis related cirrhosis mortality (p for trend=0.014). Compared to non-daily coffee drinkers, those who drank two or more cups per day had 66% reduction in mortality risk (HR=0.34, 95% CI=0.14–0.81). However, coffee intake was not associated with hepatitis B related cirrhosis mortality. The inverse relationship between caffeine intake and nonviral hepatitis-related cirrhosis mortality became null after adjustment for coffee drinking. The consumption of black tea, green tea, fruit juices or soft drinks was not associated with risk of cirrhosis death. Conclusion This study demonstrates the protective effect of coffee on non-viral hepatitis related cirrhosis mortality, and provides further impetus to evaluate coffee as a potential therapeutic agent in patients with cirrhosis. PMID:24753005
Gilligan, S B; Reich, T; Cloninger, C R
Heterogeneity in the clinical symptoms of alcohol abuse was examined in 243 men and 305 women from families of hospitalized alcoholics, who had demonstrated different patterns of inheritance of susceptibility to alcoholism. Discriminant analysis was utilized to identify nine alcoholic symptoms that distinguished male relatives of alcoholic men from those of alcoholic women. Inability to abstain from alcohol, fighting and reckless driving while intoxicated, and alcohol treatment other than Alcoholics Anonymous were more prevalent in families of male probands. Male relatives of female probands experienced later onset of loss of control over drinking associated with benders, and cirrhosis and feelings of guilt. Female relatives of alcoholic men and women showed a marked predominance of the latter (Type 1) features, whereas male relatives had different clinical features, depending on the associated mode of inheritance.
Nguyen, Van Anh; Le, Tran; Tong, Ming; Silbermann, Elizabeth; Gundogan, Fusun; de la Monte, Suzanne M.
Alcohol-related myopathy (Alc-M) is highly prevalent among heavy drinkers, although its pathogenesis is not well understood. We hypothesize that Alc-M is mediated by combined effects of insulin/IGF resistance and oxidative stress, similar to the effects of ethanol on liver and brain. We tested this hypothesis using an established model in which adult rats were pair-fed for 8 weeks with isocaloric diets containing 0% (N = 8) or 35.5% (N = 13) ethanol by caloric content. Gastrocnemius muscles were examined by histology, morphometrics, qRT-PCR analysis, and ELISAs. Chronic ethanol feeding reduced myofiber size and mRNA expression of IGF-1 polypeptide, insulin, IGF-1, and IGF-2 receptors, IRS-1, and IRS-2. Multiplex ELISAs demonstrated ethanol-associated inhibition of insulin, IRS-1, Akt, and p70S6K signaling, and increased activation of GSK-3β. In addition, ethanol-exposed muscles had increased 4-hydroxy-2-nonenal immunoreactivity, reflecting lipid peroxidation, and reduced levels of mitochondrial Complex IV, Complex V, and acetylcholinesterase. These results demonstrate that experimental Alc-M is associated with inhibition of insulin/IGF/IRS and downstream signaling that mediates metabolism and cell survival, similar to findings in alcoholic liver and brain degeneration. Moreover, the increased oxidative stress, which could be mediated by mitochondrial dysfunction, may have led to inhibition of acetylcholinesterase, which itself is sufficient to cause myofiber atrophy and degeneration. PMID:23016132
Nguyen, Van Anh; Le, Tran; Tong, Ming; Silbermann, Elizabeth; Gundogan, Fusun; de la Monte, Suzanne M
Alcohol-related myopathy (Alc-M) is highly prevalent among heavy drinkers, although its pathogenesis is not well understood. We hypothesize that Alc-M is mediated by combined effects of insulin/IGF resistance and oxidative stress, similar to the effects of ethanol on liver and brain. We tested this hypothesis using an established model in which adult rats were pair-fed for 8 weeks with isocaloric diets containing 0% (N = 8) or 35.5% (N = 13) ethanol by caloric content. Gastrocnemius muscles were examined by histology, morphometrics, qRT-PCR analysis, and ELISAs. Chronic ethanol feeding reduced myofiber size and mRNA expression of IGF-1 polypeptide, insulin, IGF-1, and IGF-2 receptors, IRS-1, and IRS-2. Multiplex ELISAs demonstrated ethanol-associated inhibition of insulin, IRS-1, Akt, and p70S6K signaling, and increased activation of GSK-3β. In addition, ethanol-exposed muscles had increased 4-hydroxy-2-nonenal immunoreactivity, reflecting lipid peroxidation, and reduced levels of mitochondrial Complex IV, Complex V, and acetylcholinesterase. These results demonstrate that experimental Alc-M is associated with inhibition of insulin/IGF/IRS and downstream signaling that mediates metabolism and cell survival, similar to findings in alcoholic liver and brain degeneration. Moreover, the increased oxidative stress, which could be mediated by mitochondrial dysfunction, may have led to inhibition of acetylcholinesterase, which itself is sufficient to cause myofiber atrophy and degeneration.
Rajaprakash, Meghna; Chakravarty, M Mallar; Lerch, Jason P; Rovet, Joanne
Introduction It is well established that individuals exposed to alcohol in utero have reduced cortical grey matter volumes. However, the candidate determinants of these reductions, cortical thickness (CT) and surface area (SA), have not been investigated exclusively in alcohol-related neurodevelopmental disorder (ARND), the most prevalent fetal alcohol spectrum disorder subgroup that lacks the characteristic facial dysmorphology. Methods T1-weighted magnetic resonance imaging scans were obtained from 88 participants (8–16 years), 36 diagnosed with ARND and 52 typically developing controls. Scans were submitted to the CIVET pipeline (version 1.1.10). Deformable models were used to construct the inner white matter surfaces and pial surfaces from which CT and SA measures were derived. Group differences in cortical volume, CT, and SA were computed using a general linear model covaried for age, sex, and handedness. Results Global cortical volume reductions in ARND did not reflect CT, which did not differ between groups. Instead, volume decreases were consistent with global SA reductions in bilateral frontal and temporal as well as right occipital regions. Local reductions in SA were observed in the right superior temporal gyrus and the right occipital-temporal region. Conclusion Results suggest that in ARND, prenatal alcohol exposure perturbs global SA to a greater degree than CT, particularly in the right temporal lobe. PMID:24653953
Sukhwal, Mahima; Suman, L N
The aim of the present study was to examine spirituality, religiosity, and alcohol-related beliefs among college students. The sample consisted of 236 college students - 120 girls and 116 boys. The age range of the sample was between 18 and 21 years. The tools used in the study were Personal Information Data Sheet, Scale for Assessment of Attitudes toward Drinking and Alcoholism (SAADA), Alcohol Expectancy Questionnaire - Adult Form (AEQ), Beliefs and Values Scale (BVS), and The Religious Background and Behavior Questionnaire (RBBQ). The data were analyzed using t-test and Pearson's product moment correlation. Higher spirituality, religiosity, and both the components of religiosity - God Consciousness and Formal Practices, were all associated with less acceptance of drinking and alcoholism. Positive affect and higher spirituality were both associated with religiosity as well as its components. A positive correlation was found among religiosity and both its components. The results revealed gender differences in that the God Consciousness component of religiosity was found to be higher in girls, but not boys, who did not have exposure to alcohol through prior use or alcohol use in family. The implications for primary prevention for college students are discussed.
Sachdeva, Ankur; Chandra, Mina; Choudhary, Mona; Dayal, Prabhoo; Anand, Kuljeet Singh
Context Alcohol consumption has escalated rapidly in many countries over the past decade. Evidence suggests a correlation between alcohol use and cognitive decline. We have systematically reviewed the concept and controversies, epidemiology, nosology, neuropathology and neurobiology, neuropsychology and management updates of alcohol-related dementia (ARD) in this paper. Evidence Acquisition We retrieved papers for this review by searching the PubMed database for terms “alcohol and dementia”, “alcohol and cognitive impairment”, and “alcohol and wernicke-korsakoff” mentioned in the title of the published papers. A total of 131 studies showed up. Appropriate studies were shortlisted and included (n = 72). Cross-references if relevant were considered from the selected studies. Eligible articles were fully read by the authors and the results were compiled. Results The prolonged and excessive use of alcohol may lead to structural and functional brain damage, leading to ARD. The cognitive deficits are most frequently observed in domains of visuospatial functions, memory and executive tasks, with a potential of partial recovery if abstinence is maintained. However, there are doubts regarding the etiopathogenesis, nosological status, prevalence and diagnostic criteria for ARD, due to difficulty in assessment and various confounding factors. Conclusions With growing cohort of young and middle-aged people, there is a probable risk of upsurge of ARD. Presently, there are dilemmas over the diagnosis of independent ARD. Thus, there is a need to develop evidence-based guidelines for diagnosis and management of ARD through further systematic studies. PMID:27818965
García-Compeán, Diego; Jáquez-Quintana, Joel O; González-González, José A; Lavalle-González, Fernando J; Villarreal-Pérez, Jesús Z; Maldonado-Garza, Hector J
The prevalence of overt diabetes mellitus (DM) in liver cirrhosis is about 30%. However, DM or impaired glucose tolerance can be observed in 90% after an oral glucose tolerance test in patients with normal fasting plasma glucose. Type 2 DM may produce cirrhosis, whereas DM may be a complication of cirrhosis. The latter is known as «hepatogenous diabetes». Overt and subclinical DM is associated with liver complications and death in cirrhotic patients. Treating diabetes is difficult in cirrhotic patients because of the metabolic impairments due to liver disease and because the most appropriate pharmacologic treatment has not been defined. It is also unknown if glycemic control with hypoglycemic agents has any impact on the course of the liver disease.
Acharya, U Rajendra; S, Vidya; Bhat, Shreya; Adeli, Hojjat; Adeli, Amir
Alcoholism is a severe disorder that affects the functionality of neurons in the central nervous system (CNS) and alters the behavior of the affected person. Electroencephalogram (EEG) signals can be used as a diagnostic tool in the evaluation of subjects with alcoholism. The neurophysiological interpretation of EEG signals in persons with alcoholism (PWA) is based on observation and interpretation of the frequency and power in their EEGs compared to EEG signals from persons without alcoholism. This paper presents a review of the known features of EEGs obtained from PWA and proposes that the impact of alcoholism on the brain can be determined by computer-aided analysis of EEGs through extracting the minute variations in the EEG signals that can differentiate the EEGs of PWA from those of nonaffected persons. The authors advance the idea of automated computer-aided diagnosis (CAD) of alcoholism by employing the EEG signals. This is achieved through judicious combination of signal processing techniques such as wavelet, nonlinear dynamics, and chaos theory and pattern recognition and classification techniques. A CAD system is cost-effective and efficient and can be used as a decision support system by physicians in the diagnosis and treatment of alcoholism especially those who do not specialize in alcoholism or neurophysiology. It can also be of great value to rehabilitation centers to assess PWA over time and to monitor the impact of treatment aimed at minimizing or reversing the effects of the disease on the brain. A CAD system can be used to determine the extent of alcoholism-related changes in EEG signals (low, medium, high) and the effectiveness of therapeutic plans.
Mellion, Michelle L.; Silbermann, Elizabeth; Gilchrist, James M.; Machan, Jason T.; Leggio, Lorenzo; de la Monte, Suzanne
Background Alcohol-related peripheral neuropathy (ALN) is generally characterized as an axonal large-fiber polyneuropathy caused by thiamine deficiency. We hypothesized, based on clinical observations, that ALN is associated with a small-fiber polyneuropathy that can be diagnosed with skin biopsy in heavy alcohol drinking subjects with normal thiamine status. Methods Eighteen individuals (9 heavy alcohol drinking subjects and 9 healthy control subjects) were assessed for the potential utility of skin biopsies in detecting ALN-associated small nerve fiber degeneration. Heavy drinking was defined as greater than 4 drinks/d and 5 drinks/d in women and men, respectively, as determined by the Timeline Follow-Back and lifetime drinking history. All subjects underwent neurological examination, nerve conduction studies, and skin biopsies to quantify end nerve fiber densities (ENFD). Other causes of neuropathy were excluded and thiamine status was assessed. Results Average ENFD were significantly decreased at the calf in the alcohol group as compared with control group (p < 0.0001). Histological sections demonstrated striking attrition and architectural simplification of intraepidermal nerve fibers in the heavy alcohol drinking subjects. There were no significant intergroup differences with respect to clinical assessments of neuropathy or thiamine status. Conclusions ALN is associated with a small-fiber neuropathy that can be detected with skin biopsy in heavy alcohol drinking individuals with normal thiamine status. Skin biopsy is a useful, minimally invasive biomarker that could extend studies to understand the effect of alcohol on the peripheral nerves and to evaluate potential therapeutic agents in larger clinical trials. PMID:24961481
Silm, Siiri; Ahas, Rein
We studied alcohol consumption and its consequences as a seasonal phenomenon in Estonia and analysed the social and environmental factors that may cause its seasonal rhythm. There are two important questions when researching the seasonality of human activities: (1) whether it is caused by natural or social factors, and (2) whether the impact of the factors is direct or indirect. Often the seasonality of social phenomena is caused by social factors, but the triggering mechanisms are related to environmental factors like temperature, precipitation, and radiation via the circannual calendar. The indicators of alcohol consumption in the current paper are grouped as: (1) pre-consumption phenomena, i.e. production, tax and excise, sales (beer, wine and vodka are analysed separately), and (2) post-consumption phenomena, i.e. alcohol-related crime and traffic accidents and the number of people detained in lockups and admitted to alcohol treatment clinics. In addition, seasonal variability in the amount of alcohol advertising has been studied, and a survey has been carried out among 87 students of Tartu University. The analysis shows that different phenomena related to alcohol have a clear seasonal rhythm in Estonia. The peak period of phenomena related to beer is in the summer, from June to August and the low point is during the first months of the year. Beer consumption correlates well with air temperature. The consumption of vodka increases sharply at the end of the year and in June; the production of vodka does not have a significant correlation with negative temperatures. The consumption of wine increases during summer and in December. The consequences of alcohol consumption, expressed as the rate of traffic accidents or the frequency of medical treatment, also show seasonal variability. Seasonal variability of alcohol consumption in Estonia is influenced by natural factors (temperature, humidity, etc.) and by social factors (celebrations, vacations, etc.). However
Boyle, Sarah C; LaBrie, Joseph W; Froidevaux, Nicole M; Witkovic, Yong D
Despite speculation that peers' alcohol-related content on social media sites (SMS) may influence the alcohol use behaviors of SMS frequenting college students, this relationship has not been investigated longitudinally. The current prospective study assesses the relationship between exposure to peers' alcohol-related SMS content and later-drinking among first-year college students. Among 408 first-year students, total exposure to peers' alcohol-related content on Facebook, Instagram, and Snapchat during the initial 6 weeks of college predicted alcohol consumption 6 months later. The rather robust relationship persisted even after students' and close friends drinking were accounted for, indicating that alcohol references on SMS do not simply reflect alcohol use behaviors that would otherwise be observed in the absence of SMS and be predictive of later alcohol use. Findings also illuminate important gender differences in the degree to which peers' alcohol-related SMS content influenced later drinking behavior as well as psychological mediators of this relationship. Among females, enhancement drinking motives and beliefs about the role of alcohol in the college experience fully mediated the relationship between SMS alcohol exposure and later drinking. Males, however, evidenced a much stronger predictive relationship between SMS alcohol exposure and second semester drinking, with this relationship only partially explained by perceptions of drinking norms, enhancement drinking motives, and beliefs about the role of alcohol in the college experience. Implications of these findings for college drinking prevention efforts and directions for future research are discussed.
Kenney, Shannon R.; Lac, Andrew; LaBrie, Joseph W.; Hummer,, Justin F.; Pham, Andy
Objective: Poor mental health, sleep problems, drinking motivations, and high-risk drinking are prevalent among college students. However, research designed to explicate the interrelationships among these health risk behaviors is lacking. This study was designed to assess the direct and indirect influences of poor mental health (a latent factor consisting of depression, anxiety, and stress) to alcohol use and alcohol-related consequences through the mediators of global sleep quality and drinking motives in a comprehensive model. Method: Participants were 1,044 heavy-drinking college students (66.3% female) who completed online surveys. Results: A hybrid structural equation model tested hypotheses involving relations leading from poor mental health to drinking motives and poorer global sleep quality to drinking outcomes. Results showed that poor mental health significantly predicted all four subscales of drinking motivations (social, coping, conformity, and enhancement) as well as poor sleep. Most of the drinking motives and poor sleep were found to explain alcohol use and negative alcohol consequences. Poor sleep predicted alcohol consequences, even after controlling for all other variables in the model. The hypothesized mediational pathways were examined with tests of indirect effects. Conclusions: This is the first study to assess concomitantly the relationships among three vital health-related domains (mental health, sleep behavior, and alcohol risk) in college students. Findings offer important implications for college personnel and interventionists interested in reducing alcohol risk by focusing on alleviating mental health problems and poor sleep quality. PMID:24172110
Chang, Koyin; Wu, Chin-Chih; Ying, Yung-Hsiang
Multiple alcohol control policies have been enacted since the early 1980s to keep drunk drivers off the roads and to prevent more alcohol-related traffic fatalities. In this paper, we analyze nine traffic policies to determine the extent to which each policy contributes to effective alcohol-related fatality prevention. Compared with the existing literature, this paper addresses a more comprehensive set of traffic policies. In addition, we used a panel GLS model that holds regional effects and state-specific time effects constant to analyze their impact on alcohol-related fatalities with two distinct rates: alcohol-related traffic deaths per capita and alcohol-related traffic deaths per total traffic deaths. While per capita alcohol-related traffic deaths is used more often in other studies, alcohol-related traffic deaths per total traffic deaths better reflects the impact of policies on deterring drunk driving. In addition, regional analyses were conducted to determine the policies that are more effective in certain regions. The findings of this study suggest that zero tolerance laws and increased beer taxes are the most effective policies in reducing alcohol-related fatalities in all regions.
Doumas, Diana M.
This study examined drinking motives as predictors of alcohol-related consequences among student athletes and nonathletes. Results indicated that the highest level of alcohol-related consequences was reported by student athletes with high levels of both coping and conformity motives. (Contains 2 tables and 2 figures.)
Isaak, Matthew I.; Perkins, David R.; Labatut, Tiffany R.
Objective: This study investigated the psychometric properties of the Disregulated Alcohol-Related Behaviors Inventory (DARBI), a measure of harmful alcohol-related behavior, and the relationship between protective behavior use and scores on the DARBI and several other measures. Participants: Participants were 281 undergraduate volunteers (60%…
Taylor, Dexter M.; Johnson, Mark B.; Voas, Robert B.; Turrisi, Robert
Restricting alcohol consumption on campus is a measure often used by college administrators to prevent alcohol abuse and-alcohol-related problems. The effect of dry campus policies on alcohol consumption and alcohol-related problems, however, remains poorly understood. This report will compare characteristics of two dry campuses with descriptions…
Forsyth, Alasdair J M; Davidson, Neil
This paper investigates the relationship between community off-sales premises and alcohol-related detritus (litter/remains) in residential neighbourhoods. This was accomplished by photographing all brand-identifiable alcohol product detritus (glass, packaging, etc.) where they lay and mapping these against the presence of off-sales outlets (licensed convenience stores) in the community. It was hypothesised that alcohol-related detritus would be greatest near to such alcohol outlets. However, although there was some evidence of a "broken bottles effect", accumulations of alcohol-related detritus near some off-sales premises, it is concluded that local area deprivation is a better predictor of such alcohol-related incivility than is outlet provision. The implications of these findings are discussed in relation to current social responsibility policy developments which are designed to make the alcohol industry liable for alcohol-related incivilities.
Romano, Eduardo O; Tippetts, A Scott; Voas, Robert B
This paper investigates the role of race/ethnicity, language skills (a proxy for acculturation among Hispanics in Arizona, California, New Mexico, and Texas), income, and education level on alcohol-related fatal motor vehicle crashes. Using the Fatality Analysis Reporting System (FARS), we confirmed previous state-based studies showing that high income and education levels have a protective influence on alcohol-related fatal motor vehicle crashes. We also confirmed that language proficiency/acculturation tends to increase the vulnerability of Hispanic women to alcohol-related fatalities. Differences in alcohol-related fatality rates across Hispanic subgroups are observed. Future reductions in alcohol-related traffic fatalities may require prevention policies that take into account existent variations in acculturation, income, and education among racial/ethnic groups and subgroups.
... of liver cancer every 6 to 12 months. Health care providers use blood tests, ultrasound, or both to check for signs of ... make the diagnosis of primary biliary cirrhosis. A health care provider uses the test selectively when he or she is concerned that ...
Zhang, Hongyu; Siegel, Christopher T.; Shuai, Ling; Lai, Jiejuan; Zeng, Linli; Zhang, Yujun; Lai, Xiangdong; Bie, Ping; Bai, Lianhua
NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2+ cells) that were isolated from healthy adult mouse liver by using a “Percoll-Plate-Wait” procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 106 cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2+ cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2+ cells may be novel adult liver progenitors that participate in liver regeneration. PMID:26905303
Francoz, Claire; Nadim, Mitra K; Durand, François
Impaired renal function due to acute kidney injury (AKI) and/or chronic kidney diseases (CKD) is frequent in cirrhosis. Recurrent episodes of AKI may occur in end-stage cirrhosis. Differential diagnosis between functional (prerenal and hepatorenal syndrome) and acute tubular necrosis (ATN) is crucial. The concept that AKI and CKD represent a continuum rather than distinct entities, is now emerging. Not all patients with AKI have a potential for full recovery. Precise evaluation of kidney function and identification of kidney changes in patients with cirrhosis is central in predicting reversibility. This review examines current biomarkers for assessing renal function and identifying the cause and mechanisms of impaired renal function. When CKD is suspected, clearance of exogenous markers is the reference to assess glomerular filtration rate, as creatinine is inaccurate and cystatin C needs further evaluation. Recent biomarkers may help differentiate ATN from hepatorenal syndrome. Neutrophil gelatinase-associated lipocalin has been the most extensively studied biomarker yet, however, there are no clear-cut values that differentiate each of these conditions. Studies comparing ATN and hepatorenal syndrome in cirrhosis, do not include a gold standard. Combinations of innovative biomarkers are attractive to identify patients justifying simultaneous liver and kidney transplantation. Accurate biomarkers of underlying CKD are lacking and kidney biopsy is often contraindicated in this population. Urinary microRNAs are attractive although not definitely validated. Efforts should be made to develop biomarkers of kidney fibrosis, a common and irreversible feature of CKD, whatever the cause. Biomarkers of maladaptative repair leading to irreversible changes and CKD after AKI are also promising.
Richardson, E.A.; Hill, S.E.; Mitchell, R.; Pearce, J.; Shortt, N.K.
Alcohol consumption may be influenced by the local alcohol retailing environment. This study is the first to examine neighbourhood alcohol outlet availability (on- and off-sales outlets) and alcohol-related health outcomes in Scotland. Alcohol-related hospitalisations and deaths were significantly higher in neighbourhoods with higher outlet densities, and off-sales outlets were more important than on-sales outlets. The relationships held for most age groups, including those under the legal minimum drinking age, although were not significant for the youngest legal drinkers (18–25 years). Alcohol-related deaths and hospitalisations were higher in more income-deprived neighbourhoods, and the gradient in deaths (but not hospitalisations) was marginally larger in neighbourhoods with higher off-sales outlet densities. Efforts to reduce alcohol-related harm should consider the potentially important role of the alcohol retail environment. PMID:25840352
Menary, Kyle R.; Corbin, William R.; Leeman, Robert F.; Fucito, Lisa M.; Toll, Benjamin A.; DeMartini, Kelly; O’Malley, Stephanie S.
Background Although drinking for tension reduction has long been posited as a risk factor for alcohol-related problems, studies investigating anxiety in relation to risk for alcohol problems have returned inconsistent results, leading researchers to search for potential moderators. Negative urgency (the tendency to become behaviorally dysregulated when experiencing negative affect) is a potential moderator of theoretical interest because it may increase risk for alcohol problems among those high in negative affect. The present study tested a cross-sectional mediated moderation hypothesis whereby an interactive effect of anxiety and negative urgency on alcohol problems is mediated through coping-related drinking motives. Method The study utilized baseline data from a hazardously drinking sample of young adults (N = 193) evaluated for participation in a randomized controlled trial of naltrexone and motivational interviewing for drinking reduction. Results The direct effect of anxiety on physiological dependence symptoms was moderated by negative urgency such that the positive association between anxiety and physiological dependence symptoms became stronger as negative urgency increased. Indirect effects of anxiety and negative urgency on alcohol problems (operating through coping motives) were also observed. Conclusions Although results of the current cross-sectional study require replication using longitudinal data, the findings suggest that the simultaneous presence of anxiety and negative urgency may be an important indicator of risk for AUDs via both direct interactive effects and indirect additive effects operating through coping motives. These findings have potentially important implications for prevention/intervention efforts for individuals who become disinhibited in the context of negative emotional states. PMID:26031346
Pabst, Alexander; Kraus, Ludwig; Piontek, Daniela; Mueller, Stefanie; Demmel, Ralf
This study investigates pathways from alcohol outcome expectancies to alcohol-related problems (ARPs), considering alcohol volume and episodic heavy drinking (EHD) as potential mediators. It is further examined whether these pathways vary by age. The population-based sample comprised 6,823 individuals aged 18 to 64 years reporting alcohol use in the past year. Direct and indirect effects of five alcohol expectancies (social assertiveness, tension reduction, sexual enhancement, cognitive impairment, aggression) and alcohol use (average daily intake, EHD) on a latent measure of ARPs (six items of the Alcohol Use Disorders Identification Test) were investigated. A multiple-group structural equation model with three age groups (18 to 24, 25 to 44, 45 to 64 years) was examined. In individuals aged 18 to 24 years, social assertiveness expectancies were positively associated with average intake and EHD, which in turn were associated with more ARPs. In addition, expectancies related to cognitive impairment and aggression were directly linked to more ARPs without mediation in this age group. In individuals aged 25 years and older, tension reduction expectancies were associated with more ARPs through increased average intake. In contrast, high scores on cognitive impairment were associated with lower average intake and in turn with fewer ARPs. Challenging expectancies of sociability in young and expectancies of relaxation in mid adulthood might help decrease high-risk drinking and subsequently ARPs. Considering negative alcohol expectancies may help to identify younger individuals at high risk for ARPs, even if they have not previously exhibited repeated excessive drinking. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
Monem, Ramey G; Fillmore, Mark T
Studies of visual attention find that drinkers spend more time attending to images of alcohol-related stimuli compared to neutral images. It is believed that this attentional bias contributes to the maintenance of alcohol use. However, no research has examined the possibility that this bias of visual attention might actually impede the functioning of other modalities, such as the processing of accompanying auditory stimuli. This study aimed to determine if alcohol-related images engender greater sensory dominance than neutral images, such that processing accompanying information from another modality (audition) would be impeded. Drinkers who had an attentional bias to alcohol-related images performed a multisensory perception task that measured how alcohol-related versus neutral visual images affected their ability to detect and respond to simultaneously presented auditory signals. In accord with the hypothesis, compared with neutral images, the presentation of alcohol-related images impaired the ability to detect and respond to auditory signals. Increased dominance of the visual modality was demonstrated by more bimodal targets being misclassified as visual-only targets in the alcohol target condition compared with that of the neutral. Findings suggest that increased processing of alcohol-related stimuli may impede an individual's ability to encode and interpret information obtained from other sensory modalities.
Iwamoto, Derek; Takamatsu, Stephanie; Castellanos, Jeanett
Binge drinking (five drinks or more in a 2-h sitting for men or four or more drinks in a 2-h sitting for women) and alcohol-related problems are a growing problem among Asian American young adults. The current study examines the sociocultural (i.e., generational status and ethnic identity) determinants of binge drinking and alcohol-related problems across U.S.-born, young-adult, Asian American ethnic groups. Data were collected from 1,575 Asian American undergraduates from a public university in Southern California. Chinese Americans consisted of the largest Asian ethnicity in the study, followed by Vietnamese, Filipino, Korean, South Asian, Japanese, Multi-Asian, and "other Asian American." Participants completed a web-based assessment of binge drinking, alcohol-related problems, ethnic identity, descriptive norms (i.e., perceived peer drinking norms), and demographic information. An analysis of variance was used to determine potential gender and ethnic differences in binge drinking and alcohol-related problems. Negative binomial regression was selected to examine the relationship between the predictors and outcomes in our model. There were no gender differences between Asian American men and women in regards to binge drinking; however, men reported more alcohol-related problems. Japanese Americans reported the highest number of binge-drinking episodes and alcohol-related problems, followed by Filipino and Multi-Asian Americans (e.g., Chinese and Korean). Living off-campus; higher scores in descriptive norms; Greek status; and belonging to the ethnic groups Japanese, Filipino, Multi-Asian, Korean, and South Asian increased the risk of engaging in binge drinking. Quantity of alcohol consumed, Greek status, gender, Filipino, South Asian, other Asian, and lower ethnic identity scores were related to alcohol-related problems. Using one of the largest samples collected to date on sociocultural determinants and drinking among U.S.-born Asian American young adults, the
Hospitalized patients with cirrhosis are at increased risk of developing bacterial infections, the most common being spontaneous bacterial peritonitis (SBP) and urinary tract infections. Independent predictors of the development of bacterial infections in hospitalized cirrhotic patients are poor liver synthetic function and admission for gastrointestinal hemorrhage. Short term (seven-day) prophylaxis with norfloxacin reduces the rate of infections and improves survival and should therefore be administered to all patients with cirrhosis and variceal hemorrhage. Cirrhotic patients who develop abdominal pain, tenderness, fever, renal failure or hepatic encephalopathy should undergo diagnostic paracentesis, and those who meet the criterion for SBP (eg, an ascites neutrophil count greater than 250/mm3) should receive antibiotics, preferably a third-generation cephalosporin. In addition to antibiotic therapy, albumin infusions have been shown to reduce the risk of renal failure and mortality in patients with SBP, particularly in those with renal dysfunction and hyperbilirubinemia at the time of diagnosis. Patients who recover from an episode of SBP should be given long term prophylaxis with norfloxacin and should be assessed for liver transplantation.
Houben, Katrijn; Nederkoorn, Chantal; Wiers, Reinout W; Jansen, Anita
According to dual-process models, excessive alcohol use emerges when response inhibition ability is insufficient to inhibit automatic impulses to drink alcohol. This study examined whether strengthening response inhibition for alcohol-related cues decreases alcohol intake. Fifty-two heavy drinking students were randomly assigned to one of two conditions: In the beer/no-go condition, participants performed a go/no-go task that consistently paired alcohol-related stimuli with a stopping response, to increase response inhibition for alcohol-related stimuli. In the beer/go condition, in contrast, participants were always required to respond to alcohol-related stimuli during the go/no-go task. Before and after the go/no-go manipulation, we measured weekly alcohol intake and implicit attitudes toward alcohol. In addition, we measured alcohol consumption during a taste test immediately after the go/no-go manipulation. Following the manipulation, participants in the beer/no-go condition demonstrated significantly increased negative implicit attitudes toward alcohol, and a significant reduction in weekly alcohol intake, while participants in the beer/go condition showed a non-significant increase in implicit positive attitudes toward alcohol and a significant increase in weekly alcohol intake. This study demonstrates that repeatedly stopping prepotent responses toward alcohol-related stimuli can be an effective strategy to reduce excessive alcohol use.
McMurran, Mary; Riemsma, Rob; Manning, Nathan; Misso, Kate; Kleijnen, Jos
Treatment programmes specifically for women offenders are under-developed. A systematic review of studies that could inform interventions for alcohol-related offending by women is reported. Three questions were addressed: 1) What is the most up to date knowledge of 'what works' with females who commit alcohol-related offences? 2) What are the identifiable risk-needs factors for non-alcohol dependent women who commit offences involving alcohol misuse? 3) Are there differences between male and female alcohol-related offending? Four studies addressed the effectiveness of psychosocial interventions; three addressed identifiable risk-needs; and 19 addressed differences between male and female offenders' alcohol-related offending. Heterogeneity of these studies precluded meta-analyses, and so a narrative synthesis method was used. There is insufficient evidence to answer the question of what treatment works with women who commit alcohol-related offences. Drunk-driving is most widely studied, and women offenders appear to have more psychosocial problems than men. Alcohol increases the likelihood of violence for both men and women, and, while the mechanisms whereby alcohol increases the likelihood of violence are likely the same in men and women, the effect may be moderated by gender-associated issues. Again, women offenders appear to have more psychosocial problems than men. Implications for developing interventions are discussed.
Kachadourian, Lorig K; Homish, Gregory G; Quigley, Brian M; Leonard, Kenneth E
The direct and interactive effects of alcohol expectancies for aggression, dispositional hostility, and heavy alcohol consumption on alcohol-related physical aggression were examined across the first four years of marriage in a sample of 634 newlywed couples. For husbands, alcohol aggression expectancies predicted increases in alcohol-related aggression; across husbands and wives, however, aggression expectancies were not found to interact with hostility or alcohol consumption to predict physical aggression. Consistent with previous research, hostility and alcohol consumption interacted with each other to predict alcohol-related aggression. Specifically, for both husbands and wives high in dispositional hostility, heavy alcohol consumption was positively associated with the occurrence of alcohol-related aggression; for those low in dispositional hostility, however, there was no association between alcohol consumption and alcohol-related aggression. Findings are contrasted with previous longitudinal research on alcohol aggression expectancies and physical aggression in married couples. The article discusses the extent to which findings may vary depending on whether expectancies are assessed in relation to alcohol's effect on one's own behavior versus alcohol's effect on others' behavior.
Pulido, José; Indave-Ruiz, B Iciar; Colell-Ortega, Esther; Ruiz-García, Mónica; Bartroli, Montserrat; Barrio, Gregorio
Based on the review of scientific papers and institutional reports on the subject and analysis of some secondary data, we assess the alcohol-related harm in Spain between 1990 and 2011. In 2011 they could be attributable to alcohol, 10% of the total mortality of the population aged 15-64, and about 30% of deaths due to traffic accidents. Among the population aged 15-64 years at least 0.8% had alcohol use disorders, an additional 5% could have harmful alcohol consumption that would need clinical evaluation, and about 20% had had some acute alcohol intoxication (AAI) in the last year. The AAI accounted for approximately 0.5-1.1 % of hospital emergency visits. Social costs of alcohol could represent 1% of gross domestic product. The prevalence of alcohol-related harm was significantly higher in men than women, with a male/female ratio greater than three for alcohol-related mortality and serious injuries, and this situation has hardly changed in the last 20 years. Alcohol-related harm has followed a downward trend, except for AAI. In 1990-2011 the standardized mortality rates related to alcohol decreased by half. Large gaps in knowledge and uncertainties on alcohol-related harm in Spanish population, clearly justify the institutional support for the research in this field and the implementation of a comprehensive monitoring system.
Background Inpatient care for alcohol intoxication is increasing in Sweden, especially among young women. Since it is well known that alcohol disorder is a chronic relapsing illness, this study examines the extent to which people return for more care. Method All inpatients with alcohol-related diagnoses in Stockholm County during 1997 were followed prospectively to 2007 through registers. The proportion reappearing for the same diagnosis, other alcohol-related inpatient, or outpatient care each year after baseline, as well as the number of years the inpatients reappeared were calculated (n = 2735). Three diagnoses were examined separately; alcohol dependence, harmful use of alcohol, and alcohol intoxication. Results Three out of five inpatients with an alcohol diagnoses reappeared for more alcohol-related inpatient care during the following decade. The proportion returning was largest the year after baseline and then decreased curvilinearly over time. The inclusion of outpatient care increased proportions, but did not change patterns. Of those with an alcohol dependence diagnosis at baseline 42 percent returned for more alcohol-related inpatient care the first, 28 percent the fifth, and 25 percent the tenth year. Corresponding proportions for harmful use and intoxication were smaller. One in five among those with an alcohol dependence returned for more than five of the ten years. Ordered logistic regressions confirmed that besides diagnosis, age and gender were independently related to the number of years returning to care. Conclusions While middle-aged males with alcohol dependence were in a revolving door, young female inpatients with intoxication diagnosis returned to a comparably lower degree. PMID:21771291
Zhang, Xueming; Huang, Yongming; Yang, Zhengpeng; Zhang, Yuguo; Zhang, Weihui; Gao, Zu-hua; Xue, Dongbo
Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including “immune response” as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma. PMID:28355233
Baccouche, Héla; Labidi, Asma; Fekih, Monia; Mahjoub, Sonia; Kaabi, Houda; Hmida, Slama; Filali, Azza; Romdhane, Neila B
Despite the prolongation of coagulation tests, recent studies reported an increased frequency of thromboembolic events in patients with cirrhosis. The aim of this study was to evaluate the haemostatic balance in cirrhotic patients through assessing the variation of pro- and anticoagulant factors and evaluating the in-vitro thrombin generation in patients with cirrhosis and in healthy patients. Fifty-one cirrhotic patients with or without thromboembolic events and 50 controls matched by age and sex were enrolled. Procoagulant (factors VII, II, V, VIII, and XII) and inhibitor (protein C, protein S and antithrombin) factor activities were determined. Thrombin generation was measured as endogenous thrombin potential (ETP). Haemostatic balance was assessed by means of both procoagulant to inhibitor coagulation factor ratios and ETP with to without protein C activation ratios. There were 24 males and 27 females. The mean age was 57.8 years [16-91 years]. Pro and anticoagulant factors were significantly lower in patients than in controls (P < 0.001) except for factor VIII and protein S. In fact factor VIII level was significantly higher in patients than in controls and protein S levels were not significantly different between patients and controls. Almost all the pro to anticoagulant factor ratios were higher in cirrhotics than in controls, especially the factor VIII to protein C ratios which increased significantly from Child Pugh A to C (P < 0.001), the ratio of ETP with to without protein C activator was higher in patients than in controls, but did not reach a significant level (0.8 vs. 0.52) There was no statistically significant difference between Child classes. When comparing patients with history of thrombosis (n = 7) to those matched by age and sex and without history of thrombosis (n = 14), the ratios were not statistically different between the two groups. Haemostatic changes in cirrhosis tend to rebalance the haemostatic system. This state often
Shah, Anish M; Malhotra, Ashish; Kothari, Shivangi; Baddoura, Walid; Depasquale, Joseph; Spira, Robert
Liver cirrhosis is generally considered irreversible but there are reports in which there is documented reversal of fibrosis/cirrhosis in various clinical conditions like Wilson's disease, hemochromatosis, primary biliary cirrhosis and autoimmune hepatitis. The subgroup of patients with autoimmune hepatitis that will have reversal of cirrhosis is not known. We present two cases with documented liver cirrhosis that had reversal of cirrhosis after treatment with immunosuppressive agents. We postulate that patients presenting with acute hepatitis and no other fibrogenic factors have higher chances of reversal of liver cirrhosis as compared to those presenting as chronic liver injury.
Johansson, Edvard; Böckerman, Petri; Prättälä, Ritva; Uutela, Antti
This paper explores the connection between alcohol-related mortality, drinking behavior, and macroeconomic conditions in Finland using both aggregate and microlevel data from recent decades. The aggregate data reveal that an improvement in economic conditions produces a decrease in alcohol-related mortality. Microlevel data show that alcohol consumption increases during economic expansion while the probability of being a drinker remains unchanged. This demonstrates that alcohol-related mortality and self-reported alcohol consumption may be delinked in the short-run business cycle context. One explanation for this paradox is that most harmful forms of drinking are not captured in survey-based data used to study the effect of macroeconomic conditions on alcohol consumption. Our evidence does not overwhelmingly support the conclusions reported for the United States that temporary economic downturns are good for health.
Park, Hee Sun; Lee, Dong Wook
Two studies are reported using the theory of planned behavior (TPB) to predict and explain joining and not joining alcohol-related social gatherings among Korean undergraduates in various engineering majors. Specifically, considering that the attitudinal component of TPB is behavioral-outcome-based, the current study investigated whether the outcomes of engaging in a behavior and of not engaging in a behavior would similarly predict intentions to engage in a behavior and intentions to not engage in a behavior. The current study also examined whether intentions to engage and intentions to not engage would be significantly related to self-reported behavior a week later. Participants in Study 1 reported TPB components (attitudes toward behavior, subjective norms, perceived behavioral control, and behavioral intentions) concerning joining alcohol-related social gatherings. Participants in Study 2 reported TPB components concerning not joining alcohol-related social gatherings. Additionally, a week later, the participants in both studies reported their participation in alcohol-related social gatherings from the past week. Generally, the results showed that the TPB components were significantly associated with undergraduates' intentions to join and intentions to not join. Specifically, conversation-related attitudes and senior-junior relationship-related attitudes were significantly related to intentions to join, and only group-related attitudes were significantly related to intentions to not join. Intentions to join and intentions to not join were not significantly related to self-reported behavior of joining alcohol-related social gatherings a week later. The findings from the current research provide some evidence that joining or not joining alcohol-related social gatherings may not be mere behavioral opposites, predictable by the presence or absence of the same behavioral outcomes. These two aspects of the behavior may require assessment of different behavioral
Gmel, Gerhard; Kuendig, Hervé; Gaume, Jacques; Daeppen, Jean-Bernard
Alcohol-related injuries are responsible for a large share of the global mortality and morbidity burden. Scant information existed, however, for Switzerland. Based on 3653 injured patients and 3519 patients attending the emergency department of the Lausanne University Hospital for other reasons, alcohol attributable fractions with regard to the alcohol consumption in the 6 hours before the injury were estimated. Among men 17% of all injures were alcohol attributable, and 12% among women. Relative risks increased in dose-response relationship with alcohol intake. Leisure time related injuries were most likely to be alcohol attributable. Most of the alcohol-related injuries occurred at already small ethanol quantities ingested.
Hughes, Clarissa; Julian, Roberta; Richman, Matthew; Mason, Ron; Long, Gillian
This paper outlines early findings from the Tasmanian-based Social Norms Analysis Project (SNAP). The Social Norms model is presented as a theoretically informed, evidence-based model for reducing alcohol-related harm in youthful populations by utilising the complex and often positive contributions peer groups make to adolescent health and…
Wattenmaker McGann, Amanda
Previous literature provides an overview of the multiple relationships between alcohol use, protective behavioral strategies (PBS), alcohol-related negative consequences, depression, and sleep problems among college students, as well as differences by individual level characteristics, such as age, gender, and race/ethnicity. The purpose of this…
Voas, Robert B.; Torres, Pedro; Romano, Eduardo; Lacey, John H.
Objective: The purpose of this study was to determine whether the relative risk of being involved in an alcohol-related crash has changed over the decade from 1996 to 2007, a period during which there has been little evidence of a reduction in the percentage of all fatal crashes involving alcohol. Method: We compared blood-alcohol information for the 2006 and 2007 crash cases (N = 6,863, 22.8% of them women) drawn from the U.S. Fatality Analysis Reporting System (FARS) with control blood-alcohol data from participants in the 2007 U.S. National Roadside Survey (N = 6,823). Risk estimates were computed and compared with those previously obtained from the 1996 FARS and roadside survey data. Results: Although the adult relative risk of being involved in a fatal alcohol-related crash apparently did not change from 1996 to 2007, the risk for involvement in an alcohol-related crash for underage women has increased to the point where it has become the same as that for underage men. Further, the risk that sober underage men will become involved in a fatal crash has doubled over the 1996–2007 period. Conclusions: Compared with estimates obtained from a decade earlier, young women in this study are at an increased risk of involvement in alcohol-related crashes. Similarly, underage sober drivers in this study are more at risk of involvement in a crash than they were a decade earlier. PMID:22456239
Diulio, Andrea R; Cero, Ian; Witte, Tracy K; Correia, Christopher J
The present study investigated the role specific types of alcohol-related problems and life satisfaction play in predicting motivation to change alcohol use. Participants were 548 college students mandated to complete a brief intervention following an alcohol-related policy violation. Using hierarchical multiple regression, we tested for the presence of interaction and quadratic effects on baseline data collected prior to the intervention. A significant interaction indicated that the relationship between a respondent's personal consequences and his/her motivation to change differs depending upon the level of concurrent social consequences. Additionally quadratic effects for abuse/dependence symptoms and life satisfaction were found. The quadratic probes suggest that abuse/dependence symptoms and poor life satisfaction are both positively associated with motivation to change for a majority of the sample; however, the nature of these relationships changes for participants with more extreme scores. Results support the utility of using a multidimensional measure of alcohol related problems and assessing non-linear relationships when assessing predictors of motivation to change. The results also suggest that the best strategies for increasing motivation may vary depending on the types of alcohol-related problems and level of life satisfaction the student is experiencing and highlight potential directions for future research.
... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Consequences for employees engaging in alcohol-related conduct. 120.221 Section 120.221 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Medicine, Attn: Drug Abatement Division (AAM-800), 800 Independence Avenue, SW., Washington, DC 20591....
... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Consequences for employees engaging in alcohol-related conduct. 120.221 Section 120.221 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION..., Office of Aerospace Medicine, Attn: Drug Abatement Division (AAM-800), 800 Independence Avenue,...
... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Consequences for employees engaging in alcohol-related conduct. 120.221 Section 120.221 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION..., Office of Aerospace Medicine, Attn: Drug Abatement Division (AAM-800), 800 Independence Avenue,...
... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Consequences for employees engaging in alcohol-related conduct. 120.221 Section 120.221 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION..., Office of Aerospace Medicine, Attn: Drug Abatement Division (AAM-800), 800 Independence Avenue,...
Cavanagh, Lucia; Obasi, Ezemenari M.
The present study applied the Go/No-Go Association Test (GNAT; Nosek & Banaji, 2001) to measure alcohol-related implicit cognitions. Additionally, it assessed the role of implicit cognitions as a potential moderator in the relationship between explicit predictors of alcohol use and hazardous drinking behavior. University undergraduate students (N = 214) completed self-report questionnaires assessing reasons for drinking and reported alcohol use. Participants also completed two GNATs assessing implicit-alcohol-related cognitions associated with attitude (good-bad) and perceived safety (safe-dangerous). As expected, participants held implicit appraisals of alcohol as ‘‘bad’’ and ‘‘dangerous’’ in the context of nonalcoholic drinks, and as ‘‘good’’ and ‘‘safe’’ in the context of licit and illicit drugs. Implicit alcohol-related cognitions moderated the relationship between drinking to cope with negative affect and hazardous drinking and drinking due to cues or craving and hazardous drinking. These findings highlight the multidimensional nature of implicit cognitions and the role of negative implicit alcohol-related associations in moderating relationships between explicit processes and subsequent alcohol use behaviors. PMID:26989352
Alberta Dept. of Education, Edmonton. Special Education Branch.
This guide provides a review of the characteristics of children with fetal alcohol syndrome (FAS) or possible prenatal alcohol-related effects (PPAE) and describes specific intervention strategies. Section 1 offers a general review of the diagnostic procedures, the prevalence of FAS and the physical, educational, and behavioral characteristics of…
Lee, Christine M.; Maggs, Jennifer L.; Neighbors, Clayton; Patrick, Megan E.
While recent attention suggests that positive and negative alcohol-related expectancies are important determinants of alcohol use, less is known about what types of consequences young people report actually experiencing when drinking alcohol. The present study (N = 742, 54% women) examined positive (Fun/Social, Relaxation/Coping, Positive Image)…
Mounteney, J.; Haugland, S.; Skutle, A.
This study focuses on a vulnerable group of pupils often missed by mainstream school surveys. It explores alcohol use and alcohol-related problems for a sample of truants of secondary school age, comparing behaviours with a school-based sample from the same geographical area. Analyses are based on a survey among truants (n = 107) and a school…
Shook, Janice; Hiestand, Brian C.
Objective: In 2003, after several post-college football game riots, multiple strategies including strict enforcement of open container laws were instituted by the authors' city and university. The authors compared alcohol-related visits to the on-campus emergency department (ED) associated with home football games in 2002 and 2006, hypothesizing…
The present paper addressed the problem of the origin of alcohol-related social norms in the Saami minority in northern Norway. Based on data from studies of comparable ethnic minorities in Greenland, North America and Australia it could be expected that alcohol use- and abuse would be more prevalent in the Saami than in the Norwegian populations of northern Norway. No data to support this hypothesis exist. On the contrary, available data suggest that drinking problems in this group are similar to those of the majority in the area. The present paper developed the hypothesis that Saami alcohol-related social norms originated in the Laestadian religious revival. The paper investigated the impact of the Laestadian culture in the formation of alcohol-related social norms. It was concluded that the Laestadian sobriety norm, and the norm of abstinence from the use of adiafora, have influenced alcohol-related behaviour in the Saami group in such a way that this group does not conform to the drinking behaviour found in comparable minorities.
Juth, Vanessa; Smyth, Joshua M.; Thompson, Kevin; Nodes, Jennifer
Research on alcohol consumption among college students is often limited by self-reported outcomes and a narrow focus of predictor factors. This study examined both traditional risk factors for alcohol use as well as broader factors (e.g., weather, seasons) in predicting objective negative outcomes of alcohol use--alcohol-related legal infractions…
Mikhailovich, Katja; George, Amanda; Rickwood, Debra; Parker, Rhian
Studies documenting the harm associated with excessive drinking amongst university students are numerous. Fewer studies have explored the experience of non-drinkers in the university setting. In 2008, 826 students aged 18-29 years responded to an online survey aiming to investigate alcohol use and alcohol related harm at an Australian university.…
Roberts, Sarah C. M.; Bond, Jason; Korcha, Rachael; Greenfield, Thomas K.
This study explores whether associations between consuming alcohol in bars and alcohol-related harms are consistent across countries and whether country-level characteristics modify associations. We hypothesized that genderedness of bar drinking modifies associations, such that odds of harms associated with bar drinking increase more rapidly in…
Howard, Donna E.; Griffin, Melinda A.; Boekeloo, Bradley O.
This study examined the psychosocial correlates of alcohol-related sexual assault. Undergraduate students (N = 551) were recruited to complete a web-based survey. The outcome was a composite of 2 items: "experienced an unwanted sexual advance" or "was the victim of sexual assault or date rape" as a result of another's alcohol use. The predictors…
Rice, Kenneth G.; Van Arsdale, Amy C.
This study investigated the association between perfectionism (categorized by adaptive perfectionistic, maladaptive perfectionistic, or nonperfectionistic groups), perceived stress, drinking alcohol to cope, and alcohol-related problems in a large sample of college students (N = 354). Maladaptive perfectionists reported significantly higher levels…
Turner, James; Bauerle, Jennifer; Keller, Adrienne
Objective: Determine rate of college student alcohol-related vehicular traffic fatalities in Virginia during 2007. Participants: Undergraduates at colleges and universities in Virginia. Methods: Institutions with membership in the American College Health Association were invited to participate in a survey. Data collected from institutional reports…
Caldeira, Valerie; Woodin, Erica M.
Alcohol-related partnAer aggression is a pervasive social problem throughout various life stages, including the transition to parenthood. Previous research shows that alcohol use is associated with partner aggression perpetration for both men and women; however, not all individuals who consume alcohol act aggressively. In this study, the…
Pedrelli, Paola; Collado, Anahi; Shapero, Benjamin G.; Brill, Charlotte; MacPherson, Laura
Objectives: Comprehensive models elucidating the intricate associations of depressive symptoms, coping motives, alcohol use, alcohol-related problems (ARPs), and gender among young adults have been scarcely examined. This study investigated relationships among these variables and the effect of gender on these pathways. Methods: College students (N…
Leahy, Matthew M.; Jouriles, Ernest N.; Walters, Scott T.
This project examined the reliability and validity of a newly developed measure of college students' receptiveness to alcohol related information and advice. Participants were 116 college students who reported having consumed alcohol at some point in their lifetime. Participants completed a measure of receptiveness to alcohol-related…
Lindgren, Kristen P; Mullins, Peter M; Neighbors, Clayton; Blayney, Jessica A
Curiosity, composed of two factors: exploration and absorption, has been previously associated with life satisfaction, life meaningfulness, and enhanced positive affect. It also shares some overlap with sensation seeking, which has been linked to alcohol use and other addictive behaviors. The present research explored the association between curiosity and college women's problematic drinking in the context of sensation seeking. Participants (79 women) completed questionnaires measuring curiosity, sensation seeking, alcohol consumption, and consequences related to alcohol consumption. A zero-inflated negative binomial model indicated that curiosity and sensation seeking accounted for unique variance in alcohol-related problems after controlling for drinking. The curiosity factors had opposing relationships to alcohol-related problems: higher scores on absorption were associated with more alcohol-related problems whereas higher scores on exploration were associated with fewer alcohol-related problems. Should findings be replicated, the curiosity factors may represent additional prevention and intervention targets. Future directions for research about curiosity and drinking and for the inclusion of positive psychology constructs in addictive behaviors research are discussed.
Gilbertson, Troy A.
This randomized experiment examines the effects of contextual information on undergraduate college student's levels of alcohol-related incident guardianship at college parties. The research is conceptualized using routine activities theory and the theory of planned behavior. The experiment examines attitudinal variations about heavy drinking…
Ahmed, Rimsha; Hustad, John T. P.; LaSalle, Linda; Borsari, Brian
Objective: The purpose of this study is to investigate whether pregaming (ie, drinking prior to a social event) is a risk factor for hospitalization. Participants: Participants (N = 516) were undergraduate students with an alcohol-related sanction. Methods: Participants completed a survey about alcohol use, as well as behaviors and experiences,…
Zhang, RuiJie; Li, Xia; Jiang, YongShuai; Liu, GuiYou; Li, ChuanXing; Zhang, Fan; Xiao, Yun; Gong, BinSheng
High-throughout single nucleotide polymorphism detection technology and the existing knowledge provide strong support for mining the disease-related haplotypes and genes. In this study, first, we apply four kinds of haplotype identification methods (Confidence Intervals, Four Gamete Tests, Solid Spine of LD and fusing method of haplotype block) into high-throughout SNP genotype data to identify blocks, then use cluster analysis to verify the effectiveness of the four methods, and select the alcoholism-related SNP haplotypes through risk analysis. Second, we establish a mapping from haplotypes to alcoholism-related genes. Third, we inquire NCBI SNP and gene databases to locate the blocks and identify the candidate genes. In the end, we make gene function annotation by KEGG, Biocarta, and GO database. We find 159 haplotype blocks, which relate to the alcoholism most possibly on chromosome 1 approximately 22, including 227 haplotypes, of which 102 SNP haplotypes may increase the risk of alcoholism. We get 121 alcoholism-related genes and verify their reliability by the functional annotation of biology. In a word, we not only can handle the SNP data easily, but also can locate the disease-related genes precisely by combining our novel strategies of mining alcoholism-related haplotypes and genes with existing knowledge framework.
Guo, Lan; Deng, Jianxiong; He, Yuan; Deng, Xueqing; Huang, Jinghui; Huang, Guoliang; Gao, Xue; Zhang, Wei-Hong; Lu, Ciyong
Abstract Alcohol misuse among adolescents is a common issue worldwide and is an emerging problem in China. This study aimed to investigate the prevalence of alcohol drinking and alcohol-related problems among Chinese adolescents and to explore their risk factors and connections. A cross-sectional study using an anonymous questionnaire was conducted among junior and senior high school students between 2010 and 2012. Data on self-reported alcohol use, alcohol-related problems, school factors, family factors, and psychosocial factors were collected. Descriptive analyses were made of the proportions of sociodemographics, family, school, and psychosocial factors. Multilevel logistic regression models were conducted to analyze the risk factors for alcohol drinking and alcohol-related problems. Of the 105,752 students who ranged in age from 9 to 21 years, the prevalence of current drinking among students was 7.3%, and 13.2% students reported having alcohol-related problems. Male students were 1.78 (95% confidence interval [CI] = 1.69–1.87) times more likely to be involved in current drinking and 1.86 (95% CI = 1.79–1.93) times more likely to have alcohol-related problems. Higher grade level students were at a higher risk of current drinking (adjusted odds ratio [AOR] = 1.09, 95% CI = 1.05–1.13) and having alcohol-related problems (AOR = 1.43, 95% CI = 1.42–1.58). Older students were more likely to report current drinking (AOR = 1.06, 95% CI = 1.04–1.17) and having alcohol-related problems (AOR = 1.83, 95% CI = 1.82–1.85). Having poor classmate relations (AOR = 1.28, 95% CI = 1.03–1.37), having poor relationships with teachers (AOR = 1.08, 95% CI = 1.00–1.16), and below average academic achievement (AOR = 1.50, 95% CI = 1.41–1.59) were positively associated with current drinking. Moreover, students with suicidal ideation were at a higher risk of current drinking (AOR = 1.70, 95% CI = 1.61–1.81) and having alcohol-related problems (AOR = 2.08, 95% CI = 1
Corrao, G.; Bagnardi, V.; Vittadini, G.; Favilli, S.
STUDY OBJECTIVE—To investigate the utility of capture-recapture methods to estimate prevalence of subjects with alcohol related disorders using multiple incomplete lists. DESIGN—This was a cross sectional study of alcohol related disorders in a large community. SETTING—During 1997 identified cases with known alcohol related disorders were independently flagged by four sources (self help volunteering groups; psychiatric ambulatory; public alcohology service; hospital discharges). PATIENTS—381 records were flagged, corresponding to 349 individual cases from a target population resident in a northern Italy area. MAIN RESULTS—The two sample capture-recapture estimates were clearly biased because of dependencies among sources. Estimates based on log-linear models showed prevalent counts ranged from 2297 (95% confidence intervals: 1524, 3794) to 2523 (95% confidence intervals: 1623, 4627) after adjustment for dependence among sources only or also for heterogeneity in catchability among age categories (< 50 and ⩾ 50 years), respectively. CONCLUSIONS—The study suggests that capture-recapture is an appropriate approach for estimating prevalence of subjects with alcohol related problems who seek or need treatment and assistance when different lists of alcoholics can be obtained from different types of agencies involved with problematic use of alcohol. Critical factors are the complexity in case definition and the analysis of heterogeneity among people. Accurate estimates are needed to plan and evaluate public health interventions. Keywords: alcohol related problems; capture-recapture; log-linear models PMID:10890872
Lizarazo, Diana; Zabala, Valerie; Tong, Ming; Longato, Lisa; de la Monte, Suzanne M.
Background and Aim Alcohol-related liver disease (ALD) is mediated in part by insulin resistance. Attendant dysregulation of lipid metabolism increases accumulation of hepatic ceramides that worsen insulin resistance and compromise the structural and functional integrity of the liver. Insulin and insulin growth factor (IGF) stimulate aspartyl-asparaginyl-β-hydroxylase (AAH), which promotes cell motility needed for structural maintenance and remodeling of the liver. AAH mediates its effects by activating Notch, and in ALD, insulin/IGF signaling, AAH, and Notch are inhibited. Method To test the hypothesis that in ALD, hepatic ceramide load contributes to impairments in insulin, AAH, and Notch signaling, control and chronic ethanol-fed adult Long–Evans rats were treated with myriocin, an inhibitor of serine palmitoyl transferase. Livers were used to assess steatohepatitis, insulin/IGF pathway activation, and expression of AAH–Notch signaling molecules. Results Chronic ethanol-fed rats had steatohepatitis with increased ceramide levels; impairments in signaling through the insulin receptor, insulin receptor substrate, and Akt; and decreased expression of AAH, Notch, Jagged, Hairy–Enhancer of Split-1, hypoxiainducible factor 1α, and proliferating cell nuclear antigen. Myriocin abrogated many of these adverse effects of ethanol, particularly hepatic ceramide accumulation, steatohepatitis, and impairments of insulin signaling through Akt, AAH, and Notch. Conclusions In ALD, the histopathology and impairments in insulin/IGF responsiveness can be substantially resolved by ceramide inhibitor treatments, even in the context of continued chronic ethanol exposure. PMID:23802886
Durand, François; Valla, Dominique
Once patients with cirrhosis experience decompensation, early mortality risk increases sharply. Liver transplantation has transformed the prognosis of decompensated cirrhosis. Child-Pugh score has been the reference for many years for assessing the prognosis of cirrhosis. However, Child-Pugh score has important limitations among which is subjective interpretation of some of its variables, making it difficult to categorize patients according to their own disease severity. The model for end-stage liver disease (MELD) score, which was originally designed for assessing the prognosis of cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), is a continuous score relying on three objective variables. Along with TIPS, MELD score proved to be a robust marker of early mortality across a wide spectrum of causes of cirrhosis, even though 10 to 20% of patients are still misclassified. MELD is especially useful for prioritizing candidates for transplantation according to a "sickest first" policy. However, MELD is not a universal prognostic marker of cirrhosis and several MELD exceptions require more specific approaches.
Bowlus, Christopher L; Gershwin, M Eric
Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by the immune mediated destruction of small intrahepatic bile duct epithelial cells leading to cholestasis and cirrhosis. The autoimmune basis of PBC is supported by the highly specific anti-mitochondrial antibodies (AMAs) and autoreactive T cells, the former being the basis for diagnosis in the vast majority of cases. Although a rare disease, the incidence rates of PBC have been increasing, possibly due to increased testing and diagnosis as opposed to a true increase in disease incidence. Presently, most cases are asymptomatic and only suspected based upon routine liver tests. Those with symptoms typically complain of pruritus and fatigue. The diagnosis of PBC is based on the presence of at least 2 of 3 key criteria including a persistently elevated serum alkaline phosphatase, the presence of serum AMAs, and liver histology consistent with PBC. Anti-nuclear antibodies specific to PBC are useful in cases in which AMAs are not detected and may indicate a more aggressive course. Ursodeoxycholic acid is the only proven therapy for PBC and in most cases can delay or prevent disease progression. However, a subgroup of patients does not adequately respond to ursodeoxycholic acid and for whom new therapies are needed.
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Brennan, Iain R
This study identifies the individual, situational, and alcohol-related factors associated with reporting violent victimization to the police. Factors positively associated with reporting included older age and incident severity (the assailant's use of a weapon, incurring injury that required attendance at an emergency department). Factors negatively associated with reporting included higher educational qualifications, assault in the nighttime economy (NTE), and drinking more than two alcoholic drinks immediately prior to victimization. It is possible that drinkers engage in "moratorium" on reporting violence in the NTE. Recognizing and reducing the acceptability of violence in the NTE may help reduce incidence of alcohol-related violence. Organizations that use police records of violence to inform practice and policy should account for uneven distributions in reporting behavior when analyzing trends in violence.
Tang, Yi-lang; Xiang, Xiao-jun; Wang, Xu-yi; Cubells, Joseph F; Babor, Thomas F; Hao, Wei
In China, alcohol consumption is increasing faster than anywhere else in the world. A steady increase in alcohol production has also been observed in the country, together with a rise in alcohol-related harm. Despite these trends, China's policies on the sale and consumption of alcoholic beverages are weak compared with those of other countries in Asia. Weakest of all are its policies on taxation, drink driving laws, alcohol sale to minors and marketing licenses. The authors of this descriptive paper draw attention to the urgent need for public health professionals and government officials in China to prioritize population surveillance, research and interventions designed to reduce alcohol use disorders. They describe China's current alcohol policies and recent trends in alcohol-related harm and highlight the need for health officials to conduct a thorough policy review from a public health perspective, using as a model the World Health Organization's global strategy to reduce the harmful use of alcohol.
Boloursaz, Samine; Nekooei, Sirous; Seilanian Toosi, Farrokh; Rezaei-Dalouei, Hossein; Davachi, Behrooz; Kazemi, Sahar
Objectives. The aim of this article is to represent the first reported case with cooccurrence of two rare alcohol related complications. Case Report. We report a 38-year-old man with chronic alcoholism who presented with both cranial and peripheral nerve palsy. On MRI examination characteristic findings of Marchiafava-Bignami disease were recognized. Discussion. Marchiafava-Bignami disease (MBD) is a rare complication of long-term, heavy alcohol abuse that has characteristic MRI findings. Acute alcohol related polyneuropathy (AARP) is another rare and not-well-understood complication of chronic alcohol abuse. We could not find any previous report of the cooccurrence of these two complications in the literature. PMID:27668107
Negrete, J C
There is agreement that physicians can play a major role in the prevention of alcohol problems among their patients and that medical schools should prepare physicians for this role by teaching three major subject areas: knowledge, attitudes and clinical skills. Despite this agreement and the acknowledged high prevalence of alcohol problems in clinical populations, medical school coverage of these problems is not proportional to their importance. Barriers to adequate coverage of alcohol problems are traditional attitudes, confusion as to whether such problems are "medical" and lack of adequate faculty role models. These problems could be remedied by encouragement and training of interested faculty members, establishment of substance abuse centres in university medical schools, integration of alcohol-related material with relevant topics in all departments and inclusion of alcohol-related questions on medical qualifying exams. PMID:2224672
Bermejo, I; Frank, F
In migrants alcohol-related problems increase with increasing age. This group, in particular, is hardly reached by alcohol-specific care offers. Thus our project aimed at the identification of target group-specific barriers to health-care use by means of a cross-sectional study (n=435). Based on these results a trans-cultural concept for alcohol prevention among elderly migrants was developed and evaluated in a cluster-randomised controlled trial (n=176).
Gauffin, Karl; Vinnerljung, Bo; Hjern, Anders
Background Alcohol misuse is an important global health determinant and a major contributor to health inequalities. We aimed to investigate the association between school performance and alcohol-related disorders in early adulthood in a longitudinal register-based national cohort study. Methods We followed a register-based national cohort of Swedish citizens born 1973–1984 (N = 948 440) from compulsory school graduation at age 15–16 to 2009. We divided the population into five groups: high school marks (> mean + 1 SD); high average (between mean and mean + 1 SD); low average (between mean and mean − 1 SD); low (< mean – 1SD); and missing. Cox proportional hazard models were used to investigate the relation between school marks at time of graduation and hospital care for alcohol-related disorders in early adulthood. Results There was a steep gradient in the risk of alcohol-related disorders related to school performance. In comparison with peers in the top category of school marks, students with low marks had adjusted hazard ratios of 8.02 [95% confidence interval (CI) 7.20 to 8.91], low average 3.02 (2.72 to 3.35) and high average 1.55 (1.39 to 1.73). The risk associated with low school marks was stronger in the male population and in the group from high socioeconomic background. Conclusions The study demonstrated a strong graded relation between low school performance and alcohol-related disorders in young adulthood. School performance should be taken into account when developing prevention programmes/policies targeting alcohol misuse among teenagers and young adults, especially if the aim is to reach high-risk groups. PMID:25797580
Weafer, Jessica; Fillmore, Mark T.
The acute impairing effects of alcohol on inhibitory control are well-established, and these disinhibiting effects are thought to play a role in its abuse potential. Alcohol impairment of inhibitory control is typically assessed in the context of arbitrary cues, yet drinking environments are comprised of an array of alcohol-related cues that are thought to influence drinking behavior. Recent evidence suggests that alcohol-related stimuli reduce behavioral control in sober drinkers, suggesting that alcohol impairment of inhibitory control might be potentiated in the context of alcohol cues. The current study tested this hypothesis by examining performance on the attentional-bias behavioral activation (ABBA) task that measures the degree to which alcohol-related stimuli can reduce inhibition of inappropriate responses in a between-subjects design. Social drinkers (N=40) performed the task in a sober condition, and then again following placebo (0.0 g/kg) and a moderate dose of alcohol (0.65 g/kg) in counter-balanced order. Inhibitory failures were greater following alcohol images compared to neutral images in sober drinkers, replicating previous findings with the ABBA task. Moreover, alcohol-related cues exacerbated alcohol impairment of inhibitory control as evidenced by more pronounced alcohol-induced disinhibition following alcohol cues compared to neutral cues. Finally, regression analyses showed that greater alcohol-induced disinhibition following alcohol cues predicted greater self-reported alcohol consumption. These findings have important implications regarding factors contributing to binge or ‘loss of control’ drinking. That is, the additive effect of disrupted control mechanisms via both alcohol-cues and the pharmacological effects of the drug could compromise an individual’s control over ongoing alcohol consumption. PMID:25134023
Chang, Jeffrey S; Hsiao, Jenn-Ren; Chen, Che-Hong
The occurrence of more than 200 diseases, including cancer, can be attributed to alcohol drinking. The global cancer deaths attributed to alcohol-consumption rose from 243,000 in 1990 to 337,400 in 2010. In 2010, cancer deaths due to alcohol consumption accounted for 4.2% of all cancer deaths. Strong epidemiological evidence has established the causal role of alcohol in the development of various cancers, including esophageal cancer, head and neck cancer, liver cancer, breast cancer, and colorectal cancer. The evidence for the association between alcohol and other cancers is inconclusive. Because of the high prevalence of ALDH2*2 allele among East Asian populations, East Asians may be more susceptible to the carcinogenic effect of alcohol, with most evidence coming from studies of esophageal cancer and head and neck cancer, while data for other cancers are more limited. The high prevalence of ALDH2*2 allele in East Asian populations may have important public health implications and may be utilized to reduce the occurrence of alcohol-related cancers among East Asians, including: 1) Identification of individuals at high risk of developing alcohol-related cancers by screening for ALDH2 polymorphism; 2) Incorporation of ALDH2 polymorphism screening into behavioral intervention program for promoting alcohol abstinence or reducing alcohol consumption; 3) Using ALDH2 polymorphism as a prognostic indicator for alcohol-related cancers; 4) Targeting ALDH2 for chemoprevention; and 5) Setting guidelines for alcohol consumption among ALDH2 deficient individuals. Future studies should evaluate whether these strategies are effective for preventing the occurrence of alcohol-related cancers.
Téllez Villajos, L; Martínez González, J; Moreira Vicente, V; Albillos Martínez, A
Pulmonary hypertension is a relatively common phenomenon in patients with hepatic cirrhosis and can appear through various mechanisms. The most characteristic scenario that binds portal and pulmonary hypertension is portopulmonary syndrome. However, hyperdynamic circulation, TIPS placement and heart failure can raise the mean pulmonary artery pressure without increasing the resistances. These conditions are not candidates for treatment with pulmonary vasodilators and require a specific therapy. A correct assessment of hemodynamic, ultrasound and clinical variables enables the differential diagnosis of each situation that produces pulmonary hypertension in patients with cirrhosis.
Monk, Rebecca L; Heim, Derek
This study aimed to contrast student and not student outcome expectancies, and explore the diversity of alcohol-related cognitions within a wider student sample. Participants (n=549) were college students (higher education-typically aged 15-18 years), university students (further education-typically aged 18-22 years) and business people (white collar professionals <50 years) who completed questionnaires in their place of work or education. Overall positive expectancies were higher in the college students than in the business or university samples. However, not all expectancy subcategories followed this pattern. Participant groups of similar age were therefore alike in some aspects of their alcohol-related cognitions but different in others. Similarly, participant groups whom are divergent in age appeared to be alike in some of their alcohol-related cognitions, such as tension reduction expectancies. Research often homogenises students as a specific sub-set of the population, this paper hi-lights that this may be an over-simplification. Furthermore, the largely exclusive focus on student groups within research in this area may also be an oversight, given the diversity of the findings demonstrated between these groups.
Gurvich, Eugenia M.; Kenna, George A.; Leggio, Lorenzo
With a better understanding of the biologic basis of alcohol dependence and the considerable financial burden of alcohol abuse and dependence, the number of alcohol-related clinical pharmacotherapy trials has been on the rise. Subsequently, the potential to find efficacious treatments is more promising. Unfortunately, alcohol-related trials face a number of challenges, as a result of the difficulties that arise from traditional and outdated methods to collect data and ensure medication adherence. Novel technology-based assessments, such as ecological momentary assessment, interactive voice response, transdermal sensor and medication-event monitoring system provide a prospective solution—albeit not without possible concerns—to the difficulties faced in alcohol-related clinical trials. Clinical trials are meant to define the efficacy of the treatment and to determine an effective and safe dosage. However, due to lack of adherence a drug could inappropriately or mistakenly be judged as ineffective for treating a specific disorder. The described technologies may be important tools to prevent false negatives in validating drug efficacy, to provide consistency in clinical trials and to improve available data regarding the study of pharmacotherapies for alcohol dependence. PMID:23955872
Bekman, Nicole M; Anderson, Kristen G; Trim, Ryan S; Metrik, Jane; Diulio, Andrea R; Myers, Mark G; Brown, Sandra A
Alcohol-related cognitions, particularly expectancies for drinking and nondrinking and motives for nondrinking, are involved in the initiation, maintenance, and cessation of alcohol use and are hypothesized to play key roles in adolescent decision making. This study explored (a) the relationships between alcohol use expectancies, nondrinking expectancies, and nondrinking motives; (b) the roles of these cognitions across hypothesized developmental stages of adolescent alcohol use; and (c) the relationships between these cognitions and recent or intended future changes in drinking behavior in a cross-sectional sample. Surveys assessing alcohol use behaviors and attitudes were administered to 1,648 high school students. Heavier drinkers reported more positive alcohol use expectancies and fewer nondrinking motives than did lighter drinkers or nondrinkers; however, nondrinking expectancies only differed between nondrinkers and rare drinkers and all subsequent drinking classes. Alcohol use expectancies, nondrinking expectancies, and nondrinking motives differentiated students who recently initiated alcohol from those who had not, while nondrinking expectancies and nondrinking motives differentiated binge-drinking students who had made recent efforts to reduce/stop their drinking from those who had not. Intentions to initiate or reduce drinking in the coming month were also associated with these alcohol-related cognitions. Drinking and nondrinking expectancies and motives for not drinking may play critical roles in decisions to alter alcohol-use behavior during adolescence. Future exploration of temporal relationships between changes in alcohol-related cognitions and behavioral decision making will be useful in the refinement of effective prevention and intervention strategies.
Lasimbang, Helen Benedict; Shoesmith, Wendy; Mohd Daud, Mohd Nazri Bin; Kaur, Nirmal; Jin, Margaret Chin Pau; Singh, Jaswant; John, Wilfred; Salumbi, Edna; Amir, Lidwina
Alcohol is the number three contributor to the burden of disease worldwide so must remain a priority health promotion issue internationally. Malaysia is a Muslim country and alcohol-related harm was not seen as a priority until recently, because it only affects a minority of the population. Sabah has more than 30 different ethnic groups, and alcohol has a traditional role in the cultural practices of many of these groups. In 2009, the Intervention Group for Alcohol Misuse (IGAM) was formed, under the umbrella of Mercy Malaysia by a group of healthcare workers, academics, members of the Clergy and people who were previously alcohol-dependent concerned about the harmful effects of excessive alcohol consumption. IGAM in collaboration with other bodies have organized public seminars, visited villages and schools, encouraged the formation of a support group and trained healthcare professionals in health promotion intervention. The focus later changed to empowering communities to find solutions to alcohol-related harm in their community in a way which is sensitive to their culture. A standard tool-kit was developed using WHO materials as a guide. Village committees were formed and adapted the toolkit according to their needs. This strategy has been shown to be effective, in that 90% of the 20 committees formed are actively and successfully involved in health promotion to reduce alcohol-related harm in their communities.
Risør, Louise Madeleine; Fenger, Mogens; Olsen, Niels Vidiendal; Møller, Søren
The main function of erythropoietin (EPO) is to maintain red blood cell mass, but in recent years, increasing evidence has suggested a wider biological role not solely related to erythropoiesis, e.g. angiogenesis and tissue protection. EPO is produced in the liver during fetal life, but the main production shifts to the kidney after birth. The liver maintains a production capacity of up to 10% of the total EPO synthesis in healthy controls, but can be up-regulated to 90-100%. However, the hepatic EPO synthesis has been shown not to be adequate for correction of anemia in the absence of renal-derived EPO. Elevated circulating EPO has been reported in a number of diseases, but data from cirrhotic patients are sparse and the level of plasma EPO in patients with cirrhosis is controversial. Cirrhosis is characterized by liver fibrosis, hepatic dysfunction and the release of proinflammatory cytokines, which lead to arterial hypotension, hepatic nephropathy and anemia. An increase in EPO due to renal hypoperfusion, hypoxia and anemia or an EPO-mediated hepato-protective and regenerative mechanism is plausible. However, poor hepatic synthesis capacity, a decreasing co-factor level and inflammatory feedback mechanisms may explain a potential insufficient EPO response in end-stage cirrhosis. Finally, the question remains as to whether a potential increase in EPO production in certain stages of cirrhosis originates from the kidney or liver. This paper aims to review contemporary aspects of EPO relating to chronic liver disease.
Ducarme, G; Bernuau, J; Luton, D
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, asymptomatic during a protracted time, characterized by changes in the small-sized bile ducts near portal spaces. The etiology of PBC is undefined, but immunologic and environmental disturbances may contribute to the disease. Infertility is often associated with PBC and cirrhosis, but pregnancy may well occur in women with PBC and without cirrhosis or in some others with compensated cirrhosis. A pluridisciplinary approach including gastroenterologists and obstetricians is recommended. The patient must be closely monitored throughout her pregnancy with maternal and routine antenatal care. Medical treatment requires ursodeoxycholic acid (UDCA). In non-cirrhotic UDCA-treated women with PBC, pregnancy often follows a normal course with vaginal delivery. In cirrhotic patients, UDCA must be continued during pregnancy, esophageal and gastric varices must be evaluated before pregnancy, and endoscopic ligature is recommended for treating large varices. Additionally, beta-blocker therapy may be associated, especially when variceal rupture occurred previously. Elective cesarean section is recommended in patients with large esophageal or gastric varices because of the potentially increased risk of variceal bleeding during maternal expulsive efforts in case of vaginal delivery.
Shah, Neeral L; Banaei, Yasmin Pourkazemi; Hojnowski, Kristen L; Cornella, Scott L
Chronic injury to the liver from a variety of different sources can result in irreversible scarring of the liver, known as cirrhosis. Cirrhosis is a major cause of morbidity and mortality in the USA, and according to the Centers for Disease Control and Prevention was responsible for 31,903 deaths in 2010 alone. It is thus of the utmost importance to appropriately manage these patients in the inpatient and outpatient setting to improve morbidity and mortality. In this review, we address four major areas of cirrhosis management: outpatient management of portal hypertension with decompensation, hepatic encephalopathy, hepatorenal syndrome, and bleeding/coagulation issues. Outpatient management covers recommendations for health care maintenance and screening. Hepatic encephalopathy encompasses a brief review of pathophysiology, treatment in the acute setting, and long-term prevention. Hepatorenal syndrome is discussed in regards to pathophysiology and treatment in the hospital setting. Finally, a discussion of the assessment of coagulation profiles in cirrhosis and recommendations for bleeding and thrombosis complications is included. These topics are not all encompassing with regard to this complicated population, but rather an overview of a few medical problems that are commonly encountered in their care.
Beck, Kenneth H.; Kasperski, Sarah J.; Caldeira, Kimberly M.; Vincent, Kathryn B.; O'Grady, Kevin E.; Arria, Amelia M.
Background: Alcohol-impaired driving is a major public health problem. National studies indicate that about 25% of college students have driven while intoxicated in the past month and an even greater percentage drive after drinking any alcohol and/or ride with an intoxicated driver. The purpose of this investigation was to examine the change in these various alcohol-related traffic risk behaviors as students progressed through their college experience. Methods: A cohort of 1,253 first-time first-year students attending a large, mid-Atlantic university were interviewed annually for four years. Repeated measures analyses were performed using generalized estimating equations (GEE) to evaluate age-related changes in prevalence and frequency of each behavior (i.e., ages 19 to 22). Results: At age 19, 17% wt of students drove while intoxicated, 42%wt drove after drinking any alcohol, and 38%wt rode with an intoxicated driver. For all three driving behaviors, prevalence and frequency increased significantly at age 21. Males were more likely to engage in these behaviors than females. To understand the possible relationship of these behaviors to changes in drinking patterns, a post-hoc analysis was conducted and revealed that while drinking frequency increased every year, frequency of drunkenness was stable for females, but increased for males. Conclusions: Alcohol-related traffic risk behaviors are quite common among college students, and take a significant upturn when students reach the age of 21. Prevention strategies targeted to the college population are needed to prevent serious consequences of these alcohol-related traffic risk behaviors. PMID:20528819
Daly, Justine B; Campbell, Elizabeth M; Wiggers, John H; Considine, Robyn J
This study aimed to determine the prevalence of responsible hospitality policies in a group of licensed premises associated with alcohol-related harm. During March 1999, 108 licensed premises with one or more police-identified alcohol-related incidents in the previous 3 months received a visit from a police officer. A 30-item audit checklist was used to determine the responsible hospitality policies being undertaken by each premises within eight policy domains: display required signage (three items); responsible host practices to prevent intoxication and under-age drinking (five items); written policies and guidelines for responsible service (three items); discouraging inappropriate promotions (three items); safe transport (two items); responsible management issues (seven items); physical environment (three items) and entry conditions (four items). No premises were undertaking all 30 items. Eighty per cent of the premises were undertaking 20 of the 30 items. All premises were undertaking at least 17 of the items. The proportion of premises undertaking individual items ranged from 16% to 100%. Premises were less likely to report having and providing written responsible hospitality documentation to staff, using door charges and having entry/re-entry rules. Significant differences between rural and urban premises were evident for four policies. Clubs were significantly more likely than hotels to have a written responsible service of alcohol policy and to clearly display codes of dress and conditions of entry. This study provides an indication of the extent and nature of responsible hospitality policies in a sample of licensed premises that are associated with a broad range of alcohol related harms. The finding that a large majority of such premises appear to adopt responsible hospitality policies suggests a need to assess the validity and reliability of tools used in the routine assessment of such policies, and of the potential for harm from licensed premises.
Bekman, Nicole M.; Anderson, Kristen G.; Trim, Ryan S.; Metrik, Jane; Diulio, Andrea R.; Myers, Mark G.; Brown, Sandra A.
Purpose Alcohol-related cognitions, particularly expectancies for drinking and non-drinking and motives for non-drinking, are involved in the initiation, maintenance, and cessation of alcohol use and are hypothesized to play key roles in adolescent decision making. This study explored (a) the relationships between alcohol use expectancies, non-drinking expectancies and non-drinking motives, (b) the roles of these cognitions across hypothesized developmental stages of adolescent alcohol use and (c) the relationships between these cognitions and recent or intended future changes in drinking behavior in a cross-sectional sample. Methods Surveys assessing alcohol use behaviors and attitudes were administered to 1648 high school students. Results Heavier drinkers reported more positive alcohol use expectancies and fewer non-drinking motives than lighter drinkers or non-drinkers, however non-drinking expectancies only differed between non- and rare- drinkers and all subsequent drinking classes. Alcohol use expectancies, non-drinking expectancies and non-drinking motives differentiated students who recently initiated alcohol from those who had not, while non-drinking expectancies and non-drinking motives differentiated binge drinking students who had made recent efforts to reduce/stop their drinking from those who had not. Intentions to initiate or reduce drinking in the coming month were also associated with these alcohol-related cognitions. Conclusion Drinking and non-drinking expectancies, and motives for not drinking may play critical roles in decisions to alter alcohol-use behavior during adolescence. Future exploration of temporal relationships between changes in alcohol-related cognitions and behavioral decision making will be useful in the refinement of effective prevention and intervention strategies. PMID:21534645
Rapley, Tim; May, Carl; Frances Kaner, Eileen
This paper describes general practitioners' (GPs) experiences of detecting and managing alcohol and alcohol-related problems in consultations. We undertook qualitative research in two phases in the North-East of England. Initially, qualitative interviews with 29 GPs explored their everyday work with patients with alcohol-related issues. We then undertook group interviews--two with GPs and one with a primary care team--where they discussed and challenged findings of the interviews. The GPs reported routinely discussing alcohol with patients with a range of alcohol-related problems. GPs believed that this work is important, but felt that until patients were willing to accept that their alcohol consumption was problematic they could achieve very little. They tentatively introduced alcohol as a potential problem, re-introduced the topic periodically, and then waited until the patient decided to change their behaviour. They were aware that they could identify and manage more patients. A lack of time and having to work with the multiple problems that patients brought to consultations were the main factors that stopped GPs managing more risky drinkers. Centrally, we compared the results of our study with [Thom, B., & Tellez, C. (1986). A difficult business-Detecting and managing alcohol-problems in general-practice. British Journal of Addiction, 81, 405-418] seminal study that was undertaken 20 years ago. We show how the intellectual, moral, emotional and practical difficulties that GPs currently face are quite similar to those faced by GPs from 20 years ago. As the definition of what could constitute abnormal alcohol consumption has expanded, so the range of consultations that they may have to negotiate these difficulties in has also expanded.
Nashold, R D; Naor, E M
Analysis of the impact of alcohol as an underlying and non-underlying cause of death in Wisconsin showed a marked increase between 1963 and 1977 in the frequency of deaths reported with mention of alcohol. The rate of deaths for which alcohol was a non-underlying cause rose more sharply during this period (2.4 per 100,000 to 9.3) than that of alcohol-related causes (4.6/100,000 to 9.0). Nearly 90 per cent of alcohol-related deaths at ages 15-24 reported alcohol as a non-underlying cause, compared to 40.7 per cent at ages 45-54 and 57 per cent at ages 75+. This proportion was higher (50.8 per cent) among males than among females (32.8 per cent). Deaths related to alcohol are attributed to a number of underlying causes in addition to alcohol. In 1975-77, nearly half of the reported alcohol-related deaths were attributed to other causes, including accidents (14.8 per cent), heart disease (14.3 per cent), respiratory diseases (4.9 per cent), suicide (3.7 per cent), and cancer (31 per cent). These percentages may reflect substantial underreporting. Comparison of motor vehicle driver death certificates with blood alcohol test reports for these drivers shows 90 per cent underreporting of alcohol on death certificates. This fact, along with other information on underreporting, shows that the approximately 650 deaths now being reported with mention of alcohol annually in Wisconsin, represent only a portion of such deaths. PMID:7294267
Doumas, Diana M; Miller, Raissa; Esp, Susan
This study examined protective behavioral strategies (PBS) as a moderator of the relationship between impulsive sensation seeking and binge drinking and alcohol-related consequences in a sample of high school seniors (N=346). Hierarchical regression analyses indicated that impulsive sensation seeking was a significant predictor of binge drinking and alcohol-related consequences and that PBS moderated these relationships. Specifically, manner of drinking moderated the relationships such that among students with high impulsive sensation seeking, those using strategies related to how they drink (e.g. avoiding rapid and excessive drinking) reported lower levels of binge drinking and alcohol-related consequences than those using fewer of these strategies. Clinical implications are discussed including using personality-targeted interventions that equip high impulsive sensation seeking adolescents with specific strategies to reduce binge drinking and alcohol-related consequences.
Cole, Jon C; Andretta, James R; McKay, Michael T
Time perspective is an individual difference variable which assesses the extent to which orientation to the past, present and future affects current behaviors. The present study investigated the viability of temporal profiles and the degree (if any) to which these predict meaningful differences in alcohol-related problems. Participants were undergraduates recruited from a University in the North West of England. Full survey data were available for 455 individuals (aged 18-25; 49.7% male) on (a) time perspective, and (b) alcohol-related problems. Four profiles emerged and were labeled Future-Positive, Present, Past Negative-Future, and Ambivalent. As hypothesized, the Future-Positive profile was associated with the best alcohol-related outcomes. The Present profile was associated with the worst outcomes. This study demonstrates that temporal profiles are associated with alcohol-related problems.
Background Excess alcohol consumption has serious adverse effects on health and violence-related harm. In the UK around 37% of men and 29% of women drink to excess and 20% and 13% report binge drinking. The potential impact on population health from a reduction in consumption is considerable. One proposed method to reduce consumption is to reduce availability through controls on alcohol outlet density. In this study we investigate the impact of a change in the density of alcohol outlets on alcohol consumption and alcohol-related harms to health in the community. Methods/Design A natural experiment of the effect of change in outlet density between 2005–09, in Wales, UK; population 2.4 million aged 16 years and over. Data on outlets are held by the 22 local authorities in Wales under The Licensing Act 2003. The study outcomes are change in (1) alcohol consumption using data from annual Welsh Health Surveys, (2) alcohol-related hospital admissions using the Patient Episode Database for Wales, (3) Accident & Emergency department attendances between midnight–6am, and (4) alcohol-related violent crime against the person, using Police data. The data will be anonymously record-linked within the Secure Anonymised Information Linkage Databank at individual and 2001 Census Lower Super Output Area levels. New methods of network analysis will be used to estimate outlet density. Longitudinal statistical analysis will use (1) multilevel ordinal models of consumption and logistic models of admissions and Accident & Emergency attendance as a function of change in individual outlet exposure, adjusting for confounding variables, and (2) spatial models of the change in counts/rates of each outcome measure and outlet density. We will assess the impact on health inequalities and will correct for population migration. Discussion This inter-disciplinary study requires expertise in epidemiology and public health, health informatics, medical statistics, geographical information science
Parrott, Dominic J.; Miller, Cameron A.
A substantial literature has identified risk factors for intoxicated aggression and the mechanisms by which these effects are exerted. This theoretical and empirical foundation is a valuable resource for the development of treatment inventions. In contrast, a comparable literature is not available to guide development of clinical interventions for intoxicated antigay aggression. To address this gap in the literature, the present article 1) identifies risk factors and mechanisms pertinent to alcohol-related antigay aggression, 2) advances predictions regarding how alcohol will increase antigay aggression, and 3) reviews societal- and individual-level considerations for intervention based upon these hypotheses. PMID:19938923
Gilbertson, Troy A
This randomized experiment examines the effects of contextual information on undergraduate college student's levels of alcohol-related incident guardianship at college parties. The research is conceptualized using routine activities theory and the theory of planned behavior. The experiment examines attitudinal variations about heavy drinking differentiated by sex, athletic status, and location of the drinking event. The sex and athletic status variables produce statistically effects on the dependent variables, while location of the drinking event is not significant. The article concludes by discussing the importance of context as it pertains to the social norms marketing strategy utilized in much college alcohol programming, and suggests a more directed marketing approach.
Barker, Jacqueline M; Torregrossa, Mary M; Taylor, Jane R
The factors underlying vulnerability to alcoholism are largely unknown. We identified in rodents an innate endophenotype predicting individual risk for alcohol-related behaviors that was associated with decreased expression of the neuroplasticity-related polysialylated neural cell adhesion molecule (PSA-NCAM). Depletion of PSA-NCAM in the ventromedial prefrontal cortex was sufficient to render mice unable to extinguish alcohol seeking, indicating a causal role of naturally occurring variation. These data suggest a mechanism of aberrant prefrontal neuroplasticity that underlies enhanced propensity for inflexible addiction-related behavior.
Kril, J J
The relative roles of alcohol toxicity, thiamine deficiency and cirrhosis of the liver in the pathogenesis of alcohol-related brain damage are unclear. Brain shrinkage and neuronal loss from four regions of the cortex was determined in 22 alcoholics with the Wernicke-Korsakoff Syndrome (WKS), cirrhosis of the liver or neither of these complications and compared to 22 age-matched non-alcoholic controls. Brain shrinkage was most marked in those alcoholics with WKS. Neuronal loss occurred only from the superior cortex and was of equal magnitude in all alcoholic subgroups. In an animal model of alcohol abuse and thiamine deficiency, neuronal loss from the cerebral cortex occurred in a time-dependent manner. Furthermore, those cells which contained the calcium-binding protein parvalbumin appeared to be preferentially damaged in this model.
DeMartini, Kelly S.; Carey, Kate B.; Lao, Kristyn; Luciano, Matthew
Perceived drinking norms have received increased attention as one determinant of high levels of college alcohol consumption and alcohol-related problems. Excessive drinking is widely visible on college campuses, and students may therefore assume that it is peer-supported (Kitts, 2003). Research into peer relations indicates that the perceived approval of important others predicts drinking behavior (Neighbors et al., 2007). Neither the use of alcohol-related protective behavioral strategies nor alcohol-related negative consequences have been investigated in terms of their perceived approval. The purpose of this study was to extend previous research on injunctive norms and assess self-other discrepancies in levels of approval for campus drinking patterns, negative alcohol-related consequences, and protective behavioral strategies. Undergraduate volunteers (n = 324, 61% female, 67% Caucasian) completed an online survey of drinking patterns; they rated comfort with overall campus drinking, and the acceptability of alcohol-related consequences and protective strategies for themselves and their close friends. As predicted, students expressed lower acceptance of consequences than their friends, and higher acceptance of alcohol-related protective strategies. We observed main effects of gender and year in school. Males and upperclassmen expressed higher acceptance of negative consequences for both self and others, and lower acceptance of protective strategies for both self and others. Implications for prevention programs are discussed. PMID:21236586
Miller, Joseph; Prichard, Ivanka; Hutchinson, Amanda; Wilson, Carlene
Consuming an unhealthy level of alcohol is a significant problem for some young women. Potential determinants of excess consumption include perceptions of usual consumption among peers-perceptions of what is "normal." The present study examined whether perceptions of social normative endorsement of drinking, operationalized by measures of perceived alcohol consumption of close friends (proximal norms), the consumption of the "average student" (distal norms), and the extent of alcohol-related content posted by peers on Facebook were related to alcohol-related attitudes and self-reported consumption. Female university students (n=129; Mage=21.48 years, SD=3.00) completed an online questionnaire assessing Facebook use, perceived alcohol-related norms, and self-reported alcohol attitudes and consumption. Perceptions of the consumption of the average female student were a negative predictor of attitudes. Positive alcohol attitudes, extent of own alcohol-related photographic posts on Facebook, average female student alcohol consumption, and report of male close friend consumption predicted self-report of own alcohol consumption. Interestingly, female close friend norms failed to predict consumption, whereas male close friend norms predicted consumption but not attitudes, suggesting the possibility of separate cognitive pathways for alcohol-related attitudes and behavior. This study builds on existing research by casting new light on predictors of alcohol-related attitudes, as well as describing the potential role of social networking sites such as Facebook in the formation of social norms and the modulation of drinking behavior.
Martens, Matthew P; Pedersen, Eric R; Smith, Ashley E; Stewart, Sherry H; O'Brien, Kerry
Research has shown that college students participating in athletics drink more than other students, yet relatively few studies have examined variables that are associated with alcohol-related outcomes among this population. The purpose of this study was to examine the relationships among trait urgency, general drinking motives and sport-related drinking motives, and both alcohol use and alcohol-related problems. Data were collected from 198 college students participating in either intercollegiate or recreational athletics at three U.S. universities. Structural equation modeling was used to examine a series of theoretically derived explanatory models. All variables included in the model were directly associated with alcohol use and/or alcohol-related problems. The specific patterns of relationships differed across the motives and trait urgency variables. Sport-related coping motives, sport-related positive reinforcement motives, and general enhancement motives had direct relationships with alcohol use, while trait urgency, general coping motives, and sport-related positive reinforcement motives had direct relationships with alcohol-related problems. Several indirect effects on alcohol use and alcohol-related problems were also found. This study suggests that general drinking motives, sport-related drinking motives, and trait urgency all serve as important predictors of alcohol-related outcomes in college athletes.
Steinmetz, Jean-Paul; Vögele, Claus; Theisen-Flies, Christiane; Federspiel, Carine; Sütterlin, Stefan
The reliable measurement of quality of life (QoL) presents a challenge in individuals with alcohol-related brain damage. This study investigated vagally mediated heart rate variability (vmHRV) as a physiological predictor of QoL. Self- and proxy ratings of QoL and dysexecutive symptoms were collected once, while vmHRV was repeatedly assessed over a 3-week period at weekly intervals in a sample of nine alcohol-related brain damaged patients. We provide robustness checks, bootstrapped correlations with confidence intervals, and standard errors for mean scores. We observed low to very low heart rate variability scores in our patients in comparison to norm values found in healthy populations. Proxy ratings of the QoL scale “subjective physical and mental performance” and everyday executive dysfunctions were strongly related to vmHRV. Better proxy-rated QoL and fewer dysexecutive symptoms were observed in those patients with higher vmHRV. Overall, patients showed low parasympathetic activation favoring the occurrence of dysfunctional emotion regulation strategies. PMID:27616894
Dickter, Cheryl L.; Forestell, Catherine A.; Hammett, Patrick J.; Young, Chelsie M.
Rationale Previous work has indicated that implicit attentional biases to alcohol-related cues are indicative of susceptibility to alcohol dependence and escape drinking, or drinking to avoid dysphoric mood or emotions. Objective The goal of the current study was to examine whether alcohol dependence and escape drinking were associated with early neural attentional biases to alcohol cues. Methods EEG data were recorded from 54 college students who reported that they regularly drank alcohol, while they viewed alcohol and control pictures that contained human content (active) or no human content (inactive). Results Those who were alcohol dependent showed more neural attentional bias to the active alcohol-related stimuli than to the matched control stimuli early in processing, as indicated by N1 amplitude. Escape drinkers showed greater neural attention to the active alcohol cues than non-escape drinkers, as measured by larger N2 amplitudes. Conclusions While alcohol dependence is associated with enhanced automatic attentional biases early in processing, escape drinking is associated with more controlled attentional biases to active alcohol cues during a relatively later stage in processing. These findings reveal important information about the time-course of attentional processing in problem drinkers and have important implications for addiction models and treatment. PMID:24292342
Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J
The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539).
Oei, T P; Young, R M
Recent literature showed that expectancies or cognitions have been proposed as a major factor in influencing the amount of alcohol an individual consumes and the behavioral consequences following consumption. However, how alcohol expectancies influence alcohol consumption is unclear; this paper reports two studies of the relationship. Study I examined the relationship between alcohol consumption and alcohol-related positive and negative self-statements in 110 social drinkers. The results showed that, in a nondrinking situation, the alcohol expectancies and variables measuring consumption and alcohol-related problems were correlated. Also, subjects who perceived their "alcoholic sets" as negative consumed more than those who perceived theirs as positive. Study II investigated changes in self-statement responding in 8 light and 8 heavy drinkers in a "normal" pub drinking situation. The results showed that alcohol-dependent self-statements in the light drinkers were relatively stable across time and between drinking and nondrinking environments. However, the alcohol-dependent self-statements of heavy drinkers became more negative during the drinking session. Furthermore, the degree and nature of such changes appeared to be related to alcohol-associated problems and consumption.
Jessica, Weafer; Fillmore, Mark T.
Rationale Poor behavioral control and heightened attentional bias toward alcohol-related stimuli have independently received considerable attention in regard to their roles in alcohol abuse. Theoretical accounts have begun to speculate as to potential reciprocal interactions between these two mechanisms that might promote excessive alcohol consumption, yet experimental evidence is lacking. Objectives The objective of the study was to integrate these two lines of research through the development of a novel laboratory task that examines the degree to which alcohol cues serve to disrupt mechanisms of behavioral control. Methods Fifty adult drinkers were recruited to perform the attentional bias–behavioral activation (ABBA) task. The ABBA task, an adaptation of traditional cued go/no-go tasks, is a reaction time model that measures the degree to which alcohol-related stimuli can increase behavioral activation of a drinker and reduce the ability to inhibit inappropriate responses. Participants also completed a novel measure of attentional bias, the scene inspection paradigm (SIP), that measures fixation time on alcohol content imbedded in complex scenes. Results As hypothesized, the proportion of inhibitory failures on the ABBA task was significantly higher following alcohol images compared to neutral images. Correlational analyses showed that heightened attentional bias on the SIP was associated with greater response activation following alcohol images on the ABBA task. Conclusions These findings suggest that alcohol stimuli serve to disrupt mechanisms of behavioral control, and that heightened attentional bias is associated with greater disruption of control mechanisms following alcohol images. PMID:22358851
Hughes, Tonda L.; Wilsnack, Sharon C.; Kantor, Lori Wolfgang
Although there are wide differences in alcohol use patterns among countries, men are consistently more likely than women to be drinkers and to drink heavily. Studies of alcohol use among sexual minorities (SMs), however, reflect a more complex picture. Such research has found higher rates of alcohol use and alcohol-related problems among SM persons than among heterosexuals and greater differences between SM and heterosexual women than between SM and heterosexual men. A variety of factors may contribute to differences in alcohol use and alcohol-related problems between men and women and between SM and heterosexual people. An improved understanding of these factors is important to guide prevention and treatment efforts. Although there is a dearth of literature on use of alcohol by SMs in many parts of the world, especially lower- and middle-income countries, we attempt to review and integrate the sparse data that are available from these lower-resourced countries. The global perspective presented in this article is the first attempt to go beyond a general review of literature in the Western world to document the gender paradox in alcohol use among heterosexuals and SMs in diverse countries worldwide. PMID:27159819
Quinn, Patrick D.; Fromme, Kim
There are important individual differences in acute subjective responses to alcohol, which have often been assessed using self-report measures. There is also evidence of meaningful between-persons variation in alcohol’s disinhibiting effects on behavior, such that some individuals become more impaired on tasks of inhibition than do others after an intoxicating dose. The degree to which subjective alcohol responses correspond with these disinhibition effects is not yet clear. In this study, we tested associations among indices of subjective alcohol responses and their correspondence with sensitivity to alcohol-related disinhibition. We recruited recent-binge-drinking emerging adults (N = 82) for a group-administered, placebo-controlled, within-subject, counterbalanced alcohol challenge in a simulated bar laboratory. Confirmatory factor analyses revealed that a two factor model with several cross-loadings explained associations among the subjective measures well, replicating a differentiation between stimulant-like and sedative-like subjective responses. Controlling sex and placebo performance, participants who reported greater subjective stimulant-like effects—but not sedative-like effects—experienced more alcohol-related disinhibition, as measured by Cued Go/No-Go Task inhibitory failures. This association was small-to-moderate in magnitude. The results of this study highlight the distinction between stimulant-like and sedative-like subjective alcohol effects. They suggest, additionally, that there may be modest commonalities between alcohol’s acute impacts on subjective stimulation and objective disinhibition. PMID:26867000
Quinn, Patrick D; Stappenbeck, Cynthia A; Fromme, Kim
Laboratory-based experimental research has demonstrated that the pharmacological effects of alcohol can increase aggressive responding. Given mixed findings and concerns regarding task validity, however, it remains uncertain whether this effect holds constant across men and women and whether variability in subjective alcohol intoxication contributes to alcohol-related aggression. In this investigation, the authors used 4 years of event-level data in a sample of 1,775 college students (140,618 total observations) to provide a test of laboratory-derived findings on the link between alcohol and aggression in an alternative methodology. They found support for several such findings: (a) Within-person increases in alcohol intoxication, as assessed by estimated blood alcohol concentrations (eBACs), were associated with increases in the probability of aggression at the drinking-episode level; (b) this association was significantly stronger among men than among women; and (c) within-person variability and between-persons individual differences in levels of subjective alcohol intoxication were associated with aggression over and beyond eBACs. Cross-methodological replication can reduce the impact of constraints specific to experimental studies on conclusions regarding alcohol's relation with aggression.
Caldeira, Valerie; Woodin, Erica M
Alcohol-related partner aggression is a pervasive social problem throughout various life stages, including the transition to parenthood. Previous research shows that alcohol use is associated with partner aggression perpetration for both men and women; however, not all individuals who consume alcohol act aggressively. In this study, the moderating effects of general social support and partner-specific support on the association between prepregnancy alcohol use and recent partner physical aggression are investigated using a community sample of 98 pregnant couples. For men, high levels of general appraisal social support (i.e., someone to talk to about one's problems) increases the strength of the association between alcohol use and aggression perpetration, whereas partner-specific emotional support serves as a buffer. For women, general social support is not a significant moderator, but high levels of partner-specific instrumental support strengthens the association between alcohol use and aggression. These results can be applied to prevention and treatment programs for alcohol-related partner aggression.
Ray, Anne E; Turrisi, Rob; Abar, Beau; Peters, Katherine E
Although heavy episodic drinkers are at risk to experience alcohol-related consequences, studies show that a large percentage of student drinkers do not experience problems as a result of their drinking. The present study was a more in-depth examination of factors beyond just drinking quantity and frequency to explain why students experience consequences. The current research examined the relationship between the use of protective behaviors, alcohol use, and alcohol related consequences, as well as the relationship between attitudinal and cognitive predictors of engaging in protective behaviors when drinking. We hypothesized there would be a significant direct effect of protective behaviors on consequences after taking into account the effect of alcohol use and that cognitive predictors, including perceived self-efficacy, perceived effectiveness, and subjective norm, would be associated with the attitude and frequency of engaging in protective behaviors. Results supported both hypotheses, indicating good model fit for all models and significant paths between constructs (p's<.05). These findings extend the literature on protective behaviors by providing insight as to their utility in preventing harm and why students choose to engage in these behaviors. Implications for interventions are also discussed.
McPeake, Joanne; Forrest, Ewan; Quasim, Tara; Kinsella, John; O'Neill, Anna
Objective To examine the impact of critical care on future alcohol-related behaviour. Further, it aimed to explore patterns of recovery for patients with and without alcohol use disorders beyond the hospital environment. Design In-depth, semistructured interviews with participants (patients) 3–7 months post intensive care discharge. Setting The setting for this study was a 20-bedded mixed intensive care unit (ICU), in a large teaching hospital in Scotland. On admission, patients were allocated to one of the three alcohol groups: low risk, harmful/hazardous and alcohol dependency. Participants 21 participants who received mechanical ventilation for greater than 3 days were interviewed between March 2013 and June 2014. Interventions None. Measurements and main results Four themes which impacted on recovery from ICU were identified in this patient group: psychological resilience, support for activities of daily living, social support and cohesion and the impact of alcohol use disorders on recovery. Participants also discussed the importance of personalised goal setting and appropriate and timely rehabilitation for alcohol-related behaviours during the critical care recovery period. Conclusions There is a significant interplay between alcohol misuse and recovery from critical illness. This study has demonstrated that at present, there is a haphazard approach to rehabilitation for patients after ICU. A more targeted rehabilitation pathway for patients leaving critical care, with specific emphasis on alcohol misuse if appropriate, requires to be generated. PMID:27048633
Tang, Yi-lang; Xiang, Xiao-jun; Wang, Xu-yi; Cubells, Joseph F; Babor, Thomas F
Abstract In China, alcohol consumption is increasing faster than anywhere else in the world. A steady increase in alcohol production has also been observed in the country, together with a rise in alcohol-related harm. Despite these trends, China’s policies on the sale and consumption of alcoholic beverages are weak compared with those of other countries in Asia. Weakest of all are its policies on taxation, drink driving laws, alcohol sale to minors and marketing licenses. The authors of this descriptive paper draw attention to the urgent need for public health professionals and government officials in China to prioritize population surveillance, research and interventions designed to reduce alcohol use disorders. They describe China’s current alcohol policies and recent trends in alcohol-related harm and highlight the need for health officials to conduct a thorough policy review from a public health perspective, using as a model the World Health Organization’s global strategy to reduce the harmful use of alcohol. PMID:23599550
Lareu, M V; Alvarez-Prechous, A; Pardiñas, C; Concheiro, L; Carracedo, A
11 genetic markers were typed in 157 individuals suffering from alcoholic cirrhosis, and compared with a random sample of healthy individuals. No significant differences were found for transferrin, specific group component, orosomucoid, esterase D, phosphogluconate dehydrogenase and adenylate kinase. Strong associations between alcoholic cirrhosis and alpha-1-antitrypsin PI*Z allele, haptoglobin HP*1 allele and acid phosphatase ACP AC phenotype were observed. The biological significance of these associations and their relationships with the development of alcoholic cirrhosis are also discussed.
Hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatation and arterial hypoxemia. HPS is reported to be present in 4% to 32% of adult patients with end-stage liver disease and in 9%-20% of children. The pathogenesis of HPS has not been clearly identified. Portal hypertension causes impairment in the perfusion of the bowel and increases the enteral translocation of Gram (-) bacteria and endotoxins. This stimulates the release of vasoactive mediators, such as tumor necrosis factor-alpha, heme oxygenase-derived carbon monoxide and nitric oxide. Genetic alterations have not been associated with this syndrome yet; however, cytokines and chemokines have been suggested to play a role. Recently, it was reported that cumulated monocytes lead to the activation of vascular endothelial growth factor-dependent signaling pathways and pulmonary angiogenesis, which plays an important role in HPS pathogenesis. At present, the most effective and only radical treatment is a liver transplant (LT). Cirrhotic patients who are on the waiting list for an LT have a shorter survival period if they develop HPS. Therefore, it is suggested that all cirrhotic cases should be followed closely for HPS and they should have priority in the waiting list. PMID:24627594
Guo, Lan; Deng, Jianxiong; He, Yuan; Deng, Xueqing; Huang, Jinghui; Huang, Guoliang; Gao, Xue; Zhang, Wei-Hong; Lu, Ciyong
Alcohol misuse among adolescents is a common issue worldwide and is an emerging problem in China. This study aimed to investigate the prevalence of alcohol drinking and alcohol-related problems among Chinese adolescents and to explore their risk factors and connections.A cross-sectional study using an anonymous questionnaire was conducted among junior and senior high school students between 2010 and 2012. Data on self-reported alcohol use, alcohol-related problems, school factors, family factors, and psychosocial factors were collected. Descriptive analyses were made of the proportions of sociodemographics, family, school, and psychosocial factors. Multilevel logistic regression models were conducted to analyze the risk factors for alcohol drinking and alcohol-related problems.Of the 105,752 students who ranged in age from 9 to 21 years, the prevalence of current drinking among students was 7.3%, and 13.2% students reported having alcohol-related problems. Male students were 1.78 (95% confidence interval [CI] = 1.69-1.87) times more likely to be involved in current drinking and 1.86 (95% CI = 1.79-1.93) times more likely to have alcohol-related problems. Higher grade level students were at a higher risk of current drinking (adjusted odds ratio [AOR] = 1.09, 95% CI = 1.05-1.13) and having alcohol-related problems (AOR = 1.43, 95% CI = 1.42-1.58). Older students were more likely to report current drinking (AOR = 1.06, 95% CI = 1.04-1.17) and having alcohol-related problems (AOR = 1.83, 95% CI = 1.82-1.85). Having poor classmate relations (AOR = 1.28, 95% CI = 1.03-1.37), having poor relationships with teachers (AOR = 1.08, 95% CI = 1.00-1.16), and below average academic achievement (AOR = 1.50, 95% CI = 1.41-1.59) were positively associated with current drinking. Moreover, students with suicidal ideation were at a higher risk of current drinking (AOR = 1.70, 95% CI = 1.61-1.81) and having alcohol-related problems (AOR = 2.08, 95% CI = 1.98-2.16). Having higher Center
Harrison, Phillip M
During the assessment of a patient with liver disease, finding the patient has decompensated cirrhosis, as defined by the presence of jaundice, ascites, variceal haemorrhage or hepatic encephalopathy, has major implications regarding management and prevention of cirrhosis-related complications, as well as consideration for a referral for liver transplantation evaluation. Prognosis is markedly worse in patients with decompensated compared with compensated cirrhosis. In general, any patient with decompensated cirrhosis should receive evaluation and medical care by a hepatologist. Since patients frequently present with more than one facet of liver decompensation, such cases pose a complex management challenge requiring input from a multidisciplinary team and close liaison with a liver transplant centre.
... Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Biliary Atresia Cirrhosis Hemochromatosis Hepatitis A through E (Viral Hepatitis) Hepatitis ...
Ahmed, Rimsha; Hustad, John T.P.; LaSalle, Linda; Borsari, Brian
Objective The purpose of this study is to investigate whether pregaming (i.e., drinking prior to a social event) is a risk factor for hospitalization. Participants Participants (N=516) were undergraduate students with an alcohol-related sanction. Method Participants completed a survey about alcohol use, as well as behaviors and experiences prior to and during the referral event. The dependent variable was whether participants received medical attention at an emergency department during the sanction event. Results Results indicated that older students, females who pregame, students with higher alcohol use screening scores, lighter drinkers, and higher numbers of drinks before the referral event all increased the odds of receiving medical attention. Pregaming alone was not significantly related to receiving medical attention in the multivariate analysis. Conclusions Female students who pregame appear to be at risk for requiring hospitalization after drinking when controlling for the number of drinks consumed. PMID:24635415
Monk, Rebecca L; Heim, Derek
The purpose of this study was to examine the effect of environmental contexts on alcohol norms, expectancies, and efficacy ratings. University students (n = 177) recruited via opportunity sampling completed questionnaires in either university lecture theaters or in a student bar. Positive social, fun, and tension reduction outcome expectancies were higher and social drink refusal self efficacy was lower in those participants questioned in a student bar relative to those questioned in a university lecture theater. These differences were found while controlling for between-groups variations in typical alcohol consumption quantities. Although hitherto largely unexamined by research, context appears to be a potentially important moderator of alcohol-related cognitions. Such findings require further exploration to inform more effective intervention approaches and have implications for the validity of existing literature.
Peel, J L; Dansereau, D F; Dees, S
The goal of the present study was to examine scenarios for using two schematic organizers--schematic knowledge maps and conceptual matrices--in integrating episodic and semantic knowledge about alcohol. Seventy students from undergraduate general psychology classes participated for course credit. Participants were assigned to either a schematic organizer group or an essay writing group. These groups were subdivided further into two treatment sequences: episodic/semantic and semantic/episodic. The episodic activity required participants to complete materials using their own alcohol-related experiences, whereas the semantic activity required participants to annotate expert materials. Assessment measures used were consumer-satisfaction questionnaires and free-recall tests. While no preferences were established for any one scenario, the episodic activities were rated higher than the semantic activities regardless of integration sequence. The semantic/episodic integration scenario did produce higher recall scores for the expert information.
Shell, Duane F.; Huang, Zhaoqing; Qian, Ling
Aim: This paper describes Chinese university students' understanding of the meaning of the alcohol-related flushing response and how they reacted to their own and someone else's flushing in a group drinking situation. Method: The researcher surveyed 530 Chinese university students about their understanding of flushing and their perception of how people respond to a person who visibly flushes while drinking alcohol. Findings: Most students did not know about the physiological cause of flushing. There were significant gender differences in both reactions to and perception of responses to a person who flushes. There was no direct relationship between flushing and drinking behaviour. Conclusions: This description of flushing behaviour and responses to a flushing person is discussed in terms of educational opportunities to change behaviours that could reduce the cancer related risks of this visibly at-risk group. PMID:25983401
Valle, Rubén; Sánchez, Elard; Perales, Alberto
In order to evaluate the frequency of depressive symptomatology (DS) and alcohol-related problems (ARP) during the academic training of medical students from Universidad Nacional Mayor de San Marcos, a cross-sectional study was conducted among students from first to sixth year of career. The Zung Self-Rating depression scale was used to evaluate DS and the CAGE questionnaire to evaluate ARP. 23.3% of participants had DS, and 7.3% had ARP. We found that the frequency of DS and ARP was higher among students in the first years of career. We recommend it is necessary to take action in the prevention and detection of these disorders from the first years of training of medical students.
Reeb, Ben T; Chan, Sut Yee Shirley; Conger, Katherine J; Martin, Monica J; Hollis, Nicole D; Serido, Joyce; Russell, Stephen T
Research increasingly finds that race/ethnicity needs to be taken into account in the modelling of associations between protective factors and adolescent drinking behaviors in order to understand family effects and promote positive youth development. The current study examined racial/ethnic variation in the prospective effects of family cohesion on adolescent alcohol-related problems using a nationally representative sample. Data were drawn from the first two waves of the National Longitudinal Study of Adolescent to Adult Health and included 10,992 (50% female) non-Hispanic Asian, non-Hispanic Black, Latino, and non-Hispanic White 7th-12th graders. Consistent with Hirschi's social control theory of youth delinquency, higher levels of family cohesion predicted lower levels of future adolescent alcohol-related problems, independent of race/ethnicity, sex, age, baseline alcohol-related problems, and family socioeconomic status. Findings from moderation analyses indicated that the magnitude of associations differed across groups such that the protective effect of family cohesion was strongest among White adolescents. For Latino adolescents, family cohesion was not associated with alcohol-related problems. Future longitudinal cross-racial/ethnic research is needed on common and unique mechanisms underlying differential associations between family processes and adolescent high-risk drinking. Understanding these processes could help improve preventive interventions, identify vulnerable subgroups, and inform health policy aimed at reducing alcohol-related health disparities.
Raczyńska, Joanna; Habior, Andrzej; Pączek, Leszek; Foroncewicz, Bartosz; Pawełas, Andrzej; Mucha, Krzysztof
Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by the presence of antimitochondrial antibodies (AMA) and progressive immune-mediated destruction of biliary ductules, which lead to cirrhosis. Theories of the PBC etiopathogenesis assume that the disease develops secondarily as an improper immunological reaction to undefined environmental and/or infectious factors in genetically predisposed individuals. Ursodeoxycholic acid (UDCA) is the only drug recommended to treat PBC; it delays the progression of liver disease, but remains only a symptomatic treatment. In the advanced stage of PBC, the treatment of choice is liver transplantation (LTx). Nowadays, PBC is the third indication for LTx, after viral-related and alcoholic liver cirrhosis. Unfortunately, PBC recurs in 21-37% of patients at 10 years after LTx, and in 43% at 15 years after LTx, with the median time to recurrence of 3-5.5 years. Diagnosis of recurrent PBC (rPBC) is based on the liver histopathology. Although various risk factors of rPBC have been investigated, the cause of the recurrence is not clear. There is no specific treatment of rPBC. Together with immunosuppression after LTx, UDCA remains the treatment of choice. New diagnostic technologies (e.g., genomics, proteomics, cell-based therapy, and clinical study of the rPBC patients) may be helpful in understanding the pathogenesis of PBC and the development of new treatment modalities.
Nusrat, Salman; Khan, Muhammad S; Fazili, Javid; Madhoun, Mohammad F
Cirrhosis results from progressive fibrosis and is the final outcome of all chronic liver disease. It is among the ten leading causes of death in United States. Cirrhosis can result in portal hypertension and/or hepatic dysfunction. Both of these either alone or in combination can lead to many complications, including ascites, varices, hepatic encephalopathy, hepatocellular carcinoma, hepatopulmonary syndrome, and coagulation disorders. Cirrhosis and its complications not only impair quality of life but also decrease survival. Managing patients with cirrhosis can be a challenge and requires an organized and systematic approach. Increasing physicians' knowledge about prevention and treatment of these potential complications is important to improve patient outcomes. A literature search of the published data was performed to provide a comprehensive review regarding the management of cirrhosis and its complications.
Nusrat, Salman; Khan, Muhammad S; Fazili, Javid; Madhoun, Mohammad F
Cirrhosis results from progressive fibrosis and is the final outcome of all chronic liver disease. It is among the ten leading causes of death in United States. Cirrhosis can result in portal hypertension and/or hepatic dysfunction. Both of these either alone or in combination can lead to many complications, including ascites, varices, hepatic encephalopathy, hepatocellular carcinoma, hepatopulmonary syndrome, and coagulation disorders. Cirrhosis and its complications not only impair quality of life but also decrease survival. Managing patients with cirrhosis can be a challenge and requires an organized and systematic approach. Increasing physicians’ knowledge about prevention and treatment of these potential complications is important to improve patient outcomes. A literature search of the published data was performed to provide a comprehensive review regarding the management of cirrhosis and its complications. PMID:24833875
Guerrero Hernández, Ignacio; Torre Delgadillo, Aldo; Vargas Vorackova, Florencia; Uribe, Misael
Intestinal microflora constitutes a symbiotic ecosystem in permanent equilibrium, composed mainly of anaerobic bacteria. However, such equilibrium may be altered by daily conditions as drug use or pathologies interfering with intestinal physiology, generating an unfavorable environment for the organism. Besides, there are factors which may cause alterations in the intestinal wall, creating the conditions for translocation or permeation of substances or bacteria. In cirrhotic patients, there are many conditions that combine to alter the amount and populations of intestinal bacteria, as well as the functional capacity of the intestinal wall to prevent the permeation of substances and bacteria. Nowadays, numerous complications associated with cirrhosis have been identified, where such mechanisms could play an important role. There is evidence that some probiotic microorganisms could restore the microbiologic and immunologic equilibrium in the intestinal wall in cirrhotic patients and help in the treatment of complications due to cirrhosis. This article has the objective to review the interactions between intestinal flora, gut permeability, and the actual role of probiotics in the field of cirrhotic patients.
Background Sexual offences are a global public health concern. Recent changes in the law in England and Wales have dramatically altered the legal landscape of sexual offences, but sexual assaults where the victim is voluntarily intoxicated by alcohol continue to have low conviction rates. Worldwide, students are high consumers of alcohol. This research aimed to compare male and female students in relation to their knowledge and attitudes about alcohol and sexual activity and to identify factors associated with being the victim of alcohol-related non-consensual sex. Methods 1,110 students completed an online questionnaire. Drinking levels were measured using the Alcohol Use Disorder Identification Test. Non-consensual sexual experiences were measured using the Sexual Experience Survey. Univariate and multivariate analyses were undertaken using chi square and backwards stepwise logistic regression respectively. Results A third of respondents had experienced alcohol-related non-consensual sex. Male and female students differed in the importance they gave to cues in deciding if a person wished to have sex with them and their understanding of the law of consent. 82.2% of women who had experienced alcohol-related non-consensual sex were hazardous drinkers compared to 62.9% who drank at lower levels (P < 0.001). Differences existed between men and women, and between those who had and had not experienced alcohol-related non-consensual sex, in relation to assessments of culpability in scenarios depicting alcohol-related intercourse. A third of respondents believed that a significant proportion of rapes were false allegations; significantly more men than women responded in this way. Conclusions Alcohol-related coerced sexual activity is a significant occurrence among students; attitudinal and knowledge differences between males and females may explain this. Educational messages that focus upon what is deemed acceptable sexual behaviour, the law and rape myths are needed but
High risk drinking is linked with high rates of physical harm. The reported incidence of alcohol - related trauma among Aboriginal and Torres Strait Islander people in the Northern Territory is the highest in the world. Facial fractures are common among young Aboriginal and Torres Strait Islanders. They are often linked with misuse of alcohol in the Northern Territory and are frequently secondary to assault. This review focuses on alcohol-related trauma in the Territory and draws attention to an urgent need for preventative health approach to address this critical issue. PMID:22862897
Wang, Jinjun; Yang, Guo-Xiang; Tsuneyama, Koichi; Gershwin, M Eric; Ridgway, William M; Leung, Patrick S C
Within the last decade, several mouse models that manifest characteristic features of primary biliary cirrhosis (PBC) with antimitochondrial antibodies (AMAs) and immune-mediated biliary duct pathology have been reported. Here, the authors discuss the current findings on two spontaneous (nonobese diabetic autoimmune biliary disease [NOD.ABD] and dominant negative transforming growth factor-β receptor II [dnTGFβRII]) and two induced (chemical xenobiotics and microbial immunization) models of PBC. These models exhibit the serological, immunological, and histopathological features of human PBC. From these animal models, it is evident that the etiology of PBC is multifactorial and requires both specific genetic predispositions and environmental insults (either xenobiotic chemicals or microbial), which lead to the breaking of tolerance and eventually liver pathology. Human PBC is likely orchestrated by multiple factors and hence no single model can fully mimic the immunopathophysiology of human PBC. Nevertheless, knowledge gained from these models has greatly advanced our understanding of the major immunological pathways as well as the etiology of PBC.
Lleo, Ana; Maroni, Luca; Glaser, Shannon; Alpini, Gianfranco; Marzioni, Marco
Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by selective destruction of intrahepatic cholangiocytes. Mechanisms underlying the development and progression of the disease are still controversial and largely undefined. Evidence suggests that PBC results from an articulated immunologic response against an immunodominant mitochondrial autoantigen, the E2 component of the pyruvate dehydrogenase complex (PDC-E2); characteristics of the disease are also the presence of disease-specific antimitochondrial autoantibodies (AMAs) and autoreactive CD4 and CD8 T cells. Recent evidence suggests that cholangiocytes show specific immunobiological features that are responsible for the selective targeting of those cells by the immune system. The immune reaction in PBC selectively targets small sized, intrahepatic bile ducts; although a specific reason for that has not been defined yet, it has been established that the biliary epithelium displays a unique heterogeneity, for which the physiological and pathophysiological features of small and large cholangiocytes significantly differ. In this review article, the authors provide a critical overview of the current evidence on the role of cholangiocytes in the immune-mediated destruction of the biliary tree that characterizes PBC.
Hoy, Anna M.; Semple, Scott I.; Mungall, Will; Lennen, Ross J.; Moran, Carmel M.; Pellicoro, Antonella; Aucott, Rebecca L.; Severin, Thomas; Saini, Rajnish; Yates, Denise; Dongre, Neelesh; Duffield, Jeremy S.; Webb, David J.; Iredale, John P.; Hayes, Peter C.
Background Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers. We hypothesized that serelaxin could ameliorate renal vasoconstriction and renal dysfunction in patients with cirrhosis and portal hypertension. Methods and findings To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v.) infusion (for 60 min at 80 μg/kg/d and then 60 min at 30 μg/kg/d) or terlipressin (single 2-mg i.v. bolus), and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min. The primary endpoint was the change from baseline in total renal artery blood flow. Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the
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Pinto, Raquel Borges; Schneider, Ana Claudia Reis; da Silveira, Themis Reverbel
Several conditions, especially chronic liver diseases, can lead to cirrhosis in children and adolescents. Most cases in clinical practice are caused by similar etiologies. In infants, cirrhosis is most often caused by biliary atresia and genetic-metabolic diseases, while in older children, it tends to result from autoimmune hepatitis, Wilson’s disease, alpha-1-antitrypsin deficiency and primary sclerosing cholangitis. The symptoms of cirrhosis in children and adolescents are similar to those of adults. However, in pediatric patients, the first sign of cirrhosis is often poor weight gain. The complications of pediatric cirrhosis are similar to those observed in adult patients, and include gastrointestinal bleeding caused by gastroesophageal varices, ascites and spontaneous bacterial peritonitis. In pediatric patients, special attention should be paid to the nutritional alterations caused by cirrhosis, since children and adolescents have higher nutritional requirements for growth and development. Children and adolescents with chronic cholestasis are at risk for several nutritional deficiencies. Malnutrition can have severe consequences for both pre- and post-liver transplant patients. The treatment of cirrhosis-induced portal hypertension in children and adolescents is mostly based on methods developed for adults. The present article will review the diagnostic and differential diagnostic aspects of end-stage liver disease in children, as well as the major treatment options for this condition. PMID:25848466
Cordova, Jonathan; Jericho, Hilary; Azzam, Ruba K
Cirrhosis is the end result of nearly all forms of progressive liver disease. The diffuse hepatic process can be characterized as a state of inflammation progressing to fibrosis and resulting in nodular regeneration, ultimately leading to disorganized liver architecture and function. The underlying etiology of cirrhosis in children may often differ from adults owing to specific disease processes that manifest in childhood, including biliary atresia, galactosemia, and neonatal hepatitis. Although basic management strategies in children are similar to those in adults, the care given to children with cirrhosis must keep the child's growth and development of paramount importance. [Pediatr Ann. 2016;45(12):e427-e432.].
Conde, Isabel; Vinaixa, Carmen; Berenguer, Marina
Chronic hepatitis C virus (HCV) infection affects around 150 million people. It is a leading cause of liver related morbidity and mortality through its predisposition to liver fibrosis, cirrhosis and end-stage liver complications. New treatments based on direct-acting antivirals have opened a new era in the management of HCV cirrhosis. They allow for HCV eradication without substantial side effects in almost all cirrhotic patients, reducing the risk of hepatocellular carcinoma, liver decompensation and mortality. This review provides an update on HCV cirrhosis. The paper focuses on the disease burden and major progresses in the diagnosis, follow-up and treatment of this patient subgroup.
Scaglione, Nichole M.; Hultgren, Brittney A.; Reavy, Racheal; Mallett, Kimberly A.; Turrisi, Rob; Cleveland, Michael J.; Sell, Nichole M.
Objective Recent studies suggest drinking protective behaviors (DPBs) and contextual protective behaviors (CPBs) can uniquely reduce alcohol-related sexual risk in college students. Few studies have examined CPBs independently, and even fewer have utilized theory to examine modifiable psychosocial predictors of students’ decisions to use CPBs. The current study used a prospective design to examine 1) rational and reactive pathways and psychosocial constructs predictive of CPB use, and 2) how gender might moderate these influences in a sample of college students. Method Students (n = 508) completed web-based baseline (mid-spring semester) and 1- and 6-month follow-up assessments of CPB use; psychosocial constructs (expectancies, normative beliefs, attitudes, and self-concept); and rational and reactive pathways (intentions and willingness). Regression was used to examine rational and reactive influences as proximal predictors of CPB use at the 6-month follow-up. Subsequent path analyses examined the effects of psychosocial constructs, as distal predictors of CPB use, mediated through the rational and reactive pathways. Results Both rational (intentions to use CPB) and reactive (willingness to use CPB) influences were significantly associated with increased CPB use. The examined distal predictors were found to effect CPB use differentially through the rational and reactive pathways. Gender did not significantly moderate any relationships within in the model. Discussion Findings suggest potential entry points for increasing CPB use that include both rational and reactive pathways. Overall, this study demonstrates the mechanisms underlying how to increase the use of CPBs in programs designed to reduce alcohol-related sexual consequences and victimization. PMID:26415062
Navarro, Héctor José; Shakeshaft, Anthony; Doran, Christopher M; Petrie, Dennis J
Approximately half of all alcohol-related crime is violent crime associated with heavy episodic drinking. Multi-component interventions are highly acceptable to communities and may be effective in reducing alcohol-related crime generally, but their impact on alcohol-related violent crime has not been examined. This study evaluated the impact and benefit-cost of a multi-component intervention (increasing community and liquor licensees' awareness, police activity, and feedback) on crimes typically associated with alcohol-related violence. The intervention was tailored to weekends identified as historically problematic in 10 experimental communities in NSW, Australia, relative to 10 control ones. There was no effect on alcohol-related assaults and a small, but statistically significant and cost-beneficial, effect on alcohol-related sexual assaults: a 64% reduction in in the experimental relative to control communities, equivalent to five fewer alcohol-related sexual assaults, with a net social benefit estimated as AUD$3,938,218. The positive benefit-cost ratio was primarily a function of the value that communities placed on reducing alcohol-related harm: the intervention would need to be more than twice as effective for its economic benefits to be comparable to its costs. It is most likely that greater reductions in crimes associated with alcohol-related violence would be achieved by a combination of complementary legislative and community-based interventions.
Andsager, Julie L.; Austin, Erica Weintraub; Pinkleton, Bruce E.
Finds that: (1) perceived realism and themes that students could identify with are important factors in increasing the salience and persuasiveness of alcohol-related public service announcements (PSAs) among undergraduate students; (2) realistic but logic-based PSAs were not as effective as unrealistic but enjoyable ads; and (3) low production…
Pedersen, Eric R.; Skidmore, Jessica R.; Aresi, Giovanni
Objective: Study abroad students are at risk for increased and problematic drinking behavior. As few efforts have been made to examine this at-risk population, the authors predicted drinking and alcohol-related consequences abroad from predeparture and site-specific factors. Participants: The sample consisted of 339 students completing study…
Doumas, Diana M.; Nelson, Kinsey; DeYoung, Amanda; Renteria, Camryn Conrad
This study evaluated the effectiveness of a web-based personalized feedback program using an objective measure of alcohol-related consequences. Participants were assigned to either the intervention group or an assessment-only control group during university orientation. Sanctions received for campus alcohol policy violations were tracked over the…
Durkin, Keith F.; Blackston, Amber; Dowd, Sabrina; Franz, Shalleigh; Eagle, Trevor
The purpose of this study was to examine the comparative influences of various protective and risk factors on the alcohol-related problems of a sample of university students. The conceptualization of these protective and risk factors in the current undertaking was informed by problem behavior theory, and draws heavily on two sociological theories…
Rothman, Emily F.; Dejong, William; Palfai, Tibor; Saitz, Richard
This study investigated the relationship between age of first drink (AFD) and a broad range of negative alcohol-related outcomes among college students exhibiting unhealthy alcohol use. We conducted an anonymous on-line survey to collect self-report data from first-year college students at a large northeastern university. Among 1,792 respondents…
Howard, Elizabeth; And Others
This teacher's manual presents lesson plans for a high-school instructional unit on Fetal Alcohol Syndrome and its less severe manifestations, Alcohol-Related Birth Defects. The lessons cover alcohol's effects during pregnancy, the history of concern about alcohol's effects, consequences of alcohol use in pregnancy, lifestyle risk reduction, and…
Caetano, Raul; Vaeth, Patrice A. C.; Rodriguez, Lori A.
The purpose of this study was to examine the association between acculturation, birthplace, and alcohol-related social problems across Hispanic national groups. A total of 5,224 Hispanic adults (18+ years) were interviewed using a multistage cluster sample design in Miami, New York, Philadelphia, Houston, and Los Angeles. Multivariate analysis…
Mallett, Kimberly A.; Varvil-Weld, Lindsey; Borsari, Brian; Read, Jennifer P.; Neighbors, Clayton; White, Helene R.
The objective of this review is to provide an update on existing research examining alcohol-related consequences among college students with relevance for individual-based interventions. While alcohol-related consequences have been a focus of study for several decades, the literature has evolved into an increasingly nuanced understanding of individual and environmental circumstances that contribute to risk for experiencing consequences. A number of risk factors for experiencing alcohol-related consequences have been identified, including belonging to specific student subgroups (e.g., Greek organizations) or drinking during high-risk periods, such as spring break. In addition, the relationship between students’ evaluations of both negative and positive consequences and their future drinking behavior has become a focus of research. The current review provides an overview of high-risk student subpopulations, high-risk windows and activities, and college students’ subjective evaluations of alcohol related consequences. Future directions for research are discussed and include determining how students’ orientations toward consequences change over time, identifying predictors of membership in high-risk consequence subgroups, and refining existing measures of consequences to address evolving research questions. PMID:23241024
Hummer, Justin F.; Pedersen, Eric R.; Mirza, Tehniat; LaBrie, Joseph W.
This study contributes to the scarce research on U.S. college students studying abroad by documenting general and sexual negative alcohol-related risks and factors associated with such risk. The manner of drinking (quantity vs. frequency), pre-departure expectations surrounding alcohol use while abroad, culture-related social anxiety, and…
Levin, Michael E.; Lillis, Jason; Seeley, John; Hayes, Steven C.; Pistorello, Jacqueline; Biglan, Anthony
Objective: This study explored the relationship of experiential avoidance (eg, the tendency to avoid, suppress, or otherwise control internal experiences even when doing so causes behavioral harm) to alcohol use disorders and alcohol-related problems. Participants: Cross-sectional data were collected from 240 undergraduate college students in…
Oscar-Berman, Marlene; Bowirrat, Abdalla
Alcoholism is a complex, multifactorial disorder involving problematic ethanol ingestion; it results from the interplay between genetic and environmental factors. Personality, likewise, is formed from a combination of inherited and acquired influences. Because selected dimensions of emotional temperament are associated with distinct neurochemical substrates contributing to specific personality phenotypes, certain aspects of abnormal emotional traits in alcoholics may be inherited. Emotions involve complex subjective experiences engaging multiple brain regions, most notably the cortex, limbic system, and cerebellum. Results of in vivo magnetic resonance imaging and post-mortem neuropathological studies of alcoholics indicate that the greatest cortical loss occurs in the frontal lobes, with concurrent thinning of the corpus callosum. Additional damage has been documented for the amygdala and hippocampus, as well as in the white matter of the cerebellum. All of the critical areas of alcoholism-related brain damage are important for normal emotional functioning. When changes occur in these brain regions, either as a consequence of chronic ethanol abuse or from a genetic anomaly affecting temperament and/or a vulnerability to alcoholism, corresponding changes in emotional functions are to be expected. In alcoholics, such changes have been observed in their perception and evaluation of emotional facial expressions, interpretation of emotional intonations in vocal utterances, and appreciation of the meaning of emotional materials. PMID:18568071
Background The incidence of mandibular fractures in the Northern Territory of Australia is very high, especially among Indigenous people. Alcohol intoxication is implicated in the majority of facial injuries, and substance use is therefore an important target for secondary prevention. The current study tests the efficacy of a brief therapy, Motivational Care Planning, in improving wellbeing and substance misuse in youth and adults hospitalised with alcohol-related facial trauma. Methods and design The study is a randomised controlled trial with 6 months of follow-up, to examine the effectiveness of a brief and culturally adapted intervention in improving outcomes for trauma patients with at-risk drinking admitted to the Royal Darwin Hospital maxillofacial surgery unit. Potential participants are identified using AUDIT-C questionnaire. Eligible participants are randomised to either Motivational Care Planning (MCP) or Treatment as Usual (TAU). The outcome measures will include quantity and frequency of alcohol and other substance use by Timeline Followback. The recruitment target is 154 participants, which with 20% dropout, is hoped to provide 124 people receiving treatment and follow-up. Discussion This project introduces screening and brief interventions for high-risk drinkers admitted to the hospital with facial trauma. It introduces a practical approach to integrating brief interventions in the hospital setting, and has potential to demonstrate significant benefits for at-risk drinkers with facial trauma. Trial Registration The trial has been registered in Australian New Zealand Clinical Trials Registry (ANZCTR) and Trial Registration: ACTRN12611000135910. PMID:23106916
Marczinski, Cecile A; Hertzenberg, Heather; Goddard, Perilou; Maloney, Sarah F; Stamates, Amy L; O'Connor, Kathleen
The purpose of this study was to determine if a brief 10-item alcohol-related Facebook® activity (ARFA) questionnaire would predict alcohol use patterns in college students (N = 146). During a single laboratory session, participants first privately logged on to their Facebook® profiles while they completed the ARFA measure, which queries past 30 day postings related to alcohol use and intoxication. Participants were then asked to complete five additional questionnaires: three measures of alcohol use (the Alcohol Use Disorders Identification Test [AUDIT], the Timeline Follow-Back [TLFB], and the Personal Drinking Habits Questionnaire [PDHQ]), the Barratt Impulsiveness Scale (BIS-11), and the Marlowe-Crowne Social Desirability Scale (MC-SDS). Regression analyses revealed that total ARFA scores were significant predictors of recent drinking behaviors, as assessed by the AUDIT, TLFB, and PDHQ measures. Moreover, impulsivity (BIS-11) and social desirability (MC-SDS) did not predict recent drinking behaviors when ARFA total scores were included in the regressions. The findings suggest that social media activity measured via the ARFA scale may be useful as a research tool for identifying risky alcohol use.
Marczinski, Cecile A.; Hertzenberg, Heather; Goddard, Perilou; Maloney, Sarah F.; Stamates, Amy L.; O’Connor, Kathleen
The purpose of this study was to determine if a brief 10-item alcohol-related Facebook® activity (ARFA) questionnaire would predict alcohol use patterns in college students (N = 146). During a single laboratory session, participants first privately logged on to their Facebook® profiles while they completed the ARFA measure, which queries past 30 day postings related to alcohol use and intoxication. Participants were then asked to complete five additional questionnaires: three measures of alcohol use (the Alcohol Use Disorders Identification Test [AUDIT], the Timeline Follow-Back [TLFB], and the Personal Drinking Habits Questionnaire [PDHQ]), the Barratt Impulsiveness Scale (BIS-11), and the Marlowe-Crowne Social Desirability Scale (MC-SDS). Regression analyses revealed that total ARFA scores were significant predictors of recent drinking behaviors, as assessed by the AUDIT, TLFB, and PDHQ measures. Moreover, impulsivity (BIS-11) and social desirability (MC-SDS) did not predict recent drinking behaviors when ARFA total scores were included in the regressions. The findings suggest that social media activity measured via the ARFA scale may be useful as a research tool for identifying risky alcohol use. PMID:28138317
Brion, Mélanie; de Timary, Philippe; Vander Stappen, Caroline; Guettat, Lamia; Lecomte, Benoît; Rombaux, Philippe; Maurage, Pierre
Chemosensory (olfaction-taste) dysfunctions are considered as reliable biomarkers in many neurological and psychiatric states. However, experimental measures of chemosensory abilities are lacking in alcohol-dependence (AD) and Korsakoff Syndrome (KS, a neurological complication of AD), despite the role played by alcohol-related odors and taste in the emergence and maintenance of AD. This study thus investigated chemosensory impairments in AD and KS. Olfactory-gustatory measures were taken among 20 KS, 20 AD, and 20 control participants. Olfaction (odor detection-discrimination-identification) was assessed using the "Sniffin Sticks" battery and taste was measured using the "Taste Strips" task. Impairments were found for high-level olfaction in AD (odor discrimination) and KS (odor discrimination-identification), even after controlling for psychopathological comorbidities. Gustatory deficits were also observed in both groups, indexing a global deficit for chemosensory perception. Finally, the gradient of impairment between the successive disease stages for odor identification suggests that the hypothesis of a continuum between AD and KS regarding cognitive deficits can be generalized to chemosensory perception. AD and KS are thus characterized by deficits in chemosensory abilities, which could constitute a marker of the AD-KS transition. In view of its deleterious influence on everyday life, chemosensory dysfunction should also be taken into account in clinical settings.
Giancola, Peter R; Parrott, Dominic J
The goals of this study were to determine the effects of past-year stimulant and sedative drug use on alcohol-related aggression and to examine whether the relation between stimulant drug use and intoxicated aggression is better accounted for by behavioral disinhibition. Participants were 330 healthy social drinkers (164 men and 166 women) between 21 and 35 years of age. Past-year stimulant and sedative use and behavioral disinhibition were assessed via self-report questionnaires. Following the consumption of either an alcohol or a placebo beverage, participants were tested on a modified version of the Taylor Aggression Paradigm [Taylor, S. (1967). Aggressive behavior and physiological arousal as a function of provocation and the tendency to inhibit aggression. Journal of Personality, 35, 297-310] in which mild electric shocks were received from, and administered to, a fictitious opponent. Aggressive behavior was operationalized as the shock intensities administered to the fictitious opponent under conditions of low and high provocation. Results indicated that alcohol significantly strengthened the relation between stimulant drug use and aggression, but only among men. Behavioral disinhibition did not account for this effect. Regardless of past-year drug use, alcohol did not facilitate aggression among women. The present findings suggest that stimulant drug use may be a risk factor for intoxicated aggression for men. However, the underlying mechanisms accounting for this effect remain unclear.
Balbo, Silvia; Brooks, Philip J
Among various potential mechanisms that could explain alcohol carcinogenicity, the metabolism of ethanol to acetaldehyde represents an obvious possible mechanism, at least in some tissues. The fundamental principle of genotoxic carcinogenesis is the formation of mutagenic DNA adducts in proliferating cells. If not repaired, these adducts can result in mutations during DNA replication, which are passed on to cells during mitosis. Consistent with a genotoxic mechanism, acetaldehyde does react with DNA to form a variety of different types of DNA adducts. In this chapter we will focus more specifically on N2-ethylidene-deoxyguanosine (N2-ethylidene-dG), the major DNA adduct formed from the reaction of acetaldehyde with DNA and specifically highlight recent data on the measurement of this DNA adduct in the human body after alcohol exposure. Because results are of particular biological relevance for alcohol-related cancer of the upper aerodigestive tract (UADT), we will also discuss the histology and cytology of the UADT, with the goal of placing the adduct data in the relevant cellular context for mechanistic interpretation. Furthermore, we will discuss the sources and concentrations of acetaldehyde and ethanol in different cell types during alcohol consumption in humans. Finally, in the last part of the chapter, we will critically evaluate the concept of carcinogenic levels of acetaldehyde, which has been raised in the literature, and discuss how data from acetaldehyde genotoxicity are and can be utilized in physiologically based models to evaluate exposure risk.
The automimmune liver disease primary biliary cirrhosis (PBC) is characterised by serum autoantibodies directed at mitochondrial and nuclear antigens (seen in most patients and a subset of patients, respectively). The antimitochondrial antibodies (AMA) characteristic of PBC are directed at members of the 2-oxoacid dehydrogenase components of multienzyme complexes; in particular, the E2 and E3 binding protein (E3BP) components of the pyruvate dehydrogenase complex (PDC). The presence of autoantibodies reactive with PDC-E2 and/or E3BP is strongly predictive of the presence of PBC. Therefore, the detection of these antibodies plays a very important role in the diagnosis of PBC. Originally demonstrated using immunofluorescence approaches, AMA can now be detected by the use of commercially available enzyme linked immunosorbent assays (ELISAs). Although the ELISA based approaches have advantages in terms of laboratory practicality, they are slightly less sensitive for the diagnosis of PBC than immunofluorescence (occasional patients with PBC show reactivity with PDC related antigens not present in the antigen preparations available for use with ELISA). Therefore, immunofluorescence should continue to be available as a complementary diagnostic test for use in occasional patients. In a subset of patients with PBC, autoantibodies are directed at increasingly well characterised nuclear antigens. Antinuclear antibody (ANA) positive patients are typically AMA negative. There are no significant differences in disease phenotype between AMA positive and AMA negative groups. At present, the clinical detection of ANA is mostly by Hep2 immunofluorescence, although ELISA kits for individual nuclear antigens are increasingly becoming available. Key Words: liver cirrhosis • biliary • autoimmunity • autoantibody PMID:11127262
Background Although there have been a wide range of epidemiological studies examining the impact of patterns of alcohol consumption among adolescents, there remains considerable variability in both defining these patterns and the ability to comprehensively evaluate their relationship to behavioural patterns. This study explores a new procedure for defining and evaluating drinking patterns and integrating well-established indicators. The composite measure is then used to estimate the impact of these patterns on alcohol-related aggressive behaviour among Italian adolescents. Methods Data were collected as part of the 2011 European School Survey Project on Alcohol and other Drugs (ESPAD). A national sample of 14,199 students aged 15–19 years was collected using an anonymous, self-administered questionnaire completed in a classroom setting. Drinking patterns were established using principal component analysis. Alcohol-related aggression was analysed as to its relationship to patterns of drinking, behaviour of friends towards alcohol use, substance use/abuse, school performance, family relationships and leisure activities. Results Several specific drinking patterns were identified: “Drinking to Excess” (DE), “Drinking with Intoxication” (DI) and “Drinking but Not to Excess” (DNE). A higher percentage of males were involved in alcohol-related aggression compared with females. In males, the DE and DI patterns significantly increased the likelihood of alcohol-related aggression, whereas the DNE pattern was negatively associated. Similar results were found in females, although the DI pattern was not significantly associated with alcohol-related aggression. Overall, cigarette smoking, illegal drug use, truancy, limited parental monitoring, frequent evenings spent outside of the home and peer influence associated strongly with alcohol-related aggression. Conclusions Our findings suggest that drinking patterns, as uniquely monitored with an integrated metric
Rodríguez Martínez, Sandra; Talaván Serna, Julio; Silvestre, Francisco-Javier
The present article makes a brief review about dental management of the patients with cirrhosis. It focus on problems related with infections, haemorrhagic events and treatment with drugs of common use in odontology.
Shevela, E Ya; Starostina, N M; Pal'tsev, A I; Shipunov, M V; Zheltova, O I; Meledina, I V; Khvan, L A; Leplina, O Yu; Ostanin, A A; Chernykh, E R; Kozlov, V A
We studied safety and clinical efficacy of transplantation of autologous bone marrow cell in complex therapy of 158 patients with chronic hepatitis and cirrhosis of the liver. The efficiency of cell therapy was assessed in 12 months after single injection of the cells. The positive response (alleviation of liver cirrhosis or stabilization of the pathological process) was observed in 70% cases. The efficacy of therapy correlated with the severity and etiology of the disease and was maximum in patients with Child-Pugh class A (in 82.5% cases) and class B liver cirrhosis (in 79% cases); in patients with class C liver cirrhosis, the positive response was achieved in 42.5% cases. In 39 patients, ultrasonic examination performed in 3 years after transplantation revealed no focal lesions or ectopic ossification foci.
Trinchet, Jean-Claude; Grando, Véronique
When it is compensated, cirrhosis is usually asymptomatic meaning that many people with the disease are unaware they have it. It is however essential to establish with certainty the cirrhosis diagnosis as the condition is responsible for a number of complications such as liver cancer (most frequently hepatocellular carcinoma), gastrointestinal bleeding or severe liver failure. Knowledge of the diagnosis ensures the prevention, screening and early treatment of these complications.
Iwamoto, Derek Kenji; Kaya, Aylin; Grivel, Margaux; Clinton, Lauren
, traditional norms that may directly pertain to hyperfemininzed Asian-American women, including modesty and sexual fidelity, may protect against heavy episodic drinking (Young et al. 2005). Conversely, the risk for heavy episodic drinking may be enhanced in men who strive to demonstrate traditional notions of masculinity through risk-taking and endorsement of playboy norms (Iwamoto et al. 2010). Although this review has illustrated the contemporary state of research on alcohol use among Asian Americans, it also highlights the significant limitations in this literature. Many of the studies reviewed here have used cross-sectional data, which do not allow researchers to infer causality between the various sociocultural factors and problematic alcohol use. One way of addressing this gap in the existing literature may be to implement longitudinal designs to further understand how the temporal relationship between sociocultural factors, including acculturation and gender norms, may impact alcohol use and alcohol-related problem trajectories. There also is a pressing need to develop greater understanding of within-group differences among U.S.-born and foreign-born Asian Americans as well as among as specific ethnic groups. To date, epidemiological research has largely neglected to examine these significant discrepancies. Given the growing prevalence of alcohol use and alcohol-related problems among Asian-American women (Grant et al. 2004; Iwamoto et al. 2010), studies also should focus on this group and explore how the intersection of gender and culture may influence alcohol use. Finally, the majority of research on this population has been conducted in college samples; therefore, it is important to also examine community samples, including U.S.-born young adults who are not attending college and older adult Asian-American populations.
Cservenka, Anita; Gillespie, Alicia J; Michael, Paul G; Nagel, Bonnie J
Objective: A family history of alcoholism is a significant risk factor for the development of alcohol use disorders (AUDs). Because common structural abnormalities are present in reward and affective brain regions in alcoholics and those with familial alcoholism, the current study examined the relationship between familial loading of AUDs and volumes of the amygdala and nucleus accumbens (NAcc) in largely alcohol-naive adolescents, ages 12–16 years (N = 140). Method: The amygdala and NAcc were delineated on each participant’s T1-weighted anatomical scan, using FMRIB Software Library’s FMRIB Integrated Registration & Segmentation Tool, and visually inspected for accuracy and volume outliers. In the 140 participants with accurate segmentation (75 male/65 female), subcortical volumes were represented as a ratio to intracranial volume (ICV). A family history density (FHD) score was calculated for each adolescent based on the presence of AUDs in first- and second-degree relatives (range: 0.03–1.50; higher scores represent a greater prevalence of familial AUDs). Multiple regressions, with age and sex controlled for, examined the association between FHD and left and right amygdala and NAcc volume/ICV. Results: There was a significant positive relationship between FHD and left NAcc volume/ICV (ΔR2 = .04, p = .02). Post hoc regressions indicated that this effect was only significant in females (ΔR2 = .11, p = .006). Conclusions: This finding suggests that the degree of familial alcoholism, genetic or otherwise, is associated with alterations in reward-related brain structure. Further work will be necessary to examine whether FHD is related to future alcohol-related problems and reward-related behaviors. PMID:25486393
Skardhamar, Torbjørn; Skirbekk, Vegard
Background Registered offenders are known to have a higher mortality rate, but given the high proportion of offenders with drug-addiction, particularly among offenders with a custodial sentence, higher mortality is expected. While the level of overall mortality compared to the non-criminal population is of interest in itself, we also estimate the risk of death by criminal records related to substance abuse and other types of criminal acts, and separate between those who receive a prison sentence or not. Methods Age-adjusted relative risks of death for 2000–2008 were studied in a population based dataset. Our dataset comprise the total Norwegian population of 2.9 million individuals aged 15–69 years old in 1999, of whom 10% had a criminal record in the 1992–1999 period. Results Individuals with a criminal record have twice the relative risk (RR) of death of the control group (non-offenders). Males with a record of use/possession of drugs and a prison record have an 11.9 RR (females, 15.6); males with a drug record but no prison record have a 6.9 RR (females 10.5). Males imprisoned for driving under the influence of substances have a 4.4 RR (females 5.6); males with a record of driving under the influence but no prison sentence have a 3.2 RR (females 6.5). Other male offenders with a prison record have a 2.8 RR (females 3.7); other male offenders with no prison record have a 1.7 RR (females 2.3). Conclusion Significantly higher mortality was found for people with a criminal record, also for those without any record of drug use. Mortality is much higher for those convicted of substance-related crimes: more so for drug- than for alcohol-related crimes and for women. PMID:24223171
Haighton, Catherine; Wilson, Graeme; Ling, Jonathan; McCabe, Karen; Crosland, Ann; Kaner, Eileen
Aims Epidemiological surveys over the last 20 years show a steady increase in the amount of alcohol consumed by older age groups. Physiological changes and an increased likelihood of health problems and medication use make older people more likely than younger age groups to suffer negative consequences of alcohol consumption, often at lower levels. However, health services targeting excessive drinking tend to be aimed at younger age groups. The aim of this study was to gain an in-depth understanding of experiences of, and attitudes towards, support for alcohol related health issues in people aged 50 and over. Methods Qualitative interviews (n = 24, 12 male/12 female, ages 51–90 years) and focus groups (n = 27, 6 male/21 female, ages 50–95 years) were carried out with a purposive sample of participants who consumed alcohol or had been dependent. Findings Participants’ alcohol misuse was often covert, isolated and carefully regulated. Participants tended to look first to their General Practitioner for help with alcohol. Detoxification courses had been found effective for dependent participants but only in the short term; rehabilitation facilities were appreciated but seen as difficult to access. Activities, informal groups and drop-in centres were endorsed. It was seen as difficult to secure treatment for alcohol and mental health problems together. Barriers to seeking help included functioning at a high level, concern about losing positive aspects of drinking, perceived stigma, service orientation to younger people, and fatalistic attitudes to help-seeking. Facilitators included concern about risk of fatal illness or pressure from significant people. Conclusion Primary care professionals need training on improving the detection and treatment of alcohol problems among older people. There is also a compelling need to ensure that aftercare is in place to prevent relapse. Strong preferences were expressed for support to be provided by those who had experienced
Foroud, T; Bucholz, K K; Edenberg, H J; Goate, A; Neuman, R J; Porjesz, B; Koller, D L; Rice, J; Reich, T; Bierut, L J; Cloninger, C R; Nurnberger, J I; Li, T K; Conneally, P M; Tischfield, J A; Crowe, R; Hesselbrock, V; Schuckit, M; Begleiter, H
There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four-class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes 3 and 4 had higher symptom endorsement probabilities than classes 1 and 2 for items reflecting severe alcohol dependence, and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met the Collaborative Study of the Genetics of Alcoholism, and >99% met ICD-10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15 cM interval.
Bobak, Martin; Malyutina, Sofia; Horvat, Pia; Pajak, Andrzej; Tamosiunas, Abdonas; Kubinova, Ruzena; Simonova, Galina; Topor-Madry, Roman; Peasey, Anne; Pikhart, Hynek; Marmot, Michael G
Alcohol has been implicated in the high mortality in Central and Eastern Europe but the magnitude of its effect, and whether it is due to regular high intake or episodic binge drinking remain unclear. The aim of this paper was to estimate the contribution of alcohol to mortality in four Central and Eastern European countries. We used data from the Health, Alcohol and Psychosocial factors in Eastern Europe is a prospective multi-centre cohort study in Novosibirsk (Russia), Krakow (Poland), Kaunas (Lithuania) and six Czech towns. Random population samples of 34,304 men and women aged 45-69 years in 2002-2005 were followed up for a median 7 years. Drinking volume, frequency and pattern were estimated from the graduated frequency questionnaire. Deaths were ascertained using mortality registers. In 230,246 person-years of follow-up, 2895 participants died from all causes, 1222 from cardiovascular diseases (CVD), 672 from coronary heart disease (CHD) and 489 from pre-defined alcohol-related causes (ARD). In fully-adjusted models, abstainers had 30-50% increased mortality risk compared to light-to-moderate drinkers. Adjusted hazard ratios (HR) in men drinking on average ≥60 g of ethanol/day (3% of men) were 1.23 (95% CI 0.95-1.59) for all-cause, 1.38 (0.95-2.02) for CVD, 1.64 (1.02-2.64) for CHD and 2.03 (1.28-3.23) for ARD mortality. Corresponding HRs in women drinking on average ≥20 g/day (2% of women) were 1.92 (1.25-2.93), 1.74 (0.76-3.99), 1.39 (0.34-5.76) and 3.00 (1.26-7.10). Binge drinking increased ARD mortality in men only. Mortality was associated with high average alcohol intake but not binge drinking, except for ARD in men.
Coomber, Kerri; Mayshak, Richelle; Hyder, Shannon; Droste, Nicolas; Curtis, Ashlee; Pennay, Amy; Gilmore, William; Lam, Tina; Chikritzhs, Tanya; Miller, Peter G.
This study examined the relationship between patron demographics, substance use, and experience of recent alcohol-related accidents and injuries that were not due to interpersonal violence in night-time entertainment districts. Cross-sectional interviews (n = 4016) were conducted around licensed venues in entertainment districts of five Australian cities. Demographic factors associated with non-violent alcohol-related injuries were examined, including gender, age, and occupation. The association between substance use on the night of interview; blood alcohol concentration (BAC), pre-drinking, energy drink consumption, and illicit drug use; and experience of injury was also explored. Thirteen percent of participants reported an alcohol-related injury within the past three months. Respondents aged younger than 25 years were significantly more likely to report an alcohol-related injury. Further, a significant occupation effect was found indicating the rate of alcohol-related injury was lower in managers/professionals compared to non-office workers. The likelihood of prior alcohol-related injury significantly increased with BAC, and self-reported pre-drinking, energy drink, or illicit drug consumption on the night of interview. These findings provide an indication of the demographic and substance use-related associations with alcohol-related injuries and, therefore, potential avenues of population-level policy intervention. Policy responses to alcohol-related harm must also account for an assessment and costing of non-violent injuries. PMID:28085105
Adams, Jerry; And Others
A set of two pamphlets is presented on the topic of Fetal Alcohol Syndrome and Alcohol-Related Birth Defects. "Ten Projects for Preventing Fetal Alcohol Syndrome and Other Alcohol-Related Birth Defects" provides ideas and materials for students and others to use in educating the public about the dangers of alcohol use during pregnancy.…
McKellar, John; Stewart, Eric; Humphreys, Keith
A positive corelation between Alcoholics Anonymous (AA) involvement and better alcohol-related outcomes has been identified in research studies, but whether this correlation reflects a causal relationship remains a subject of meaningful debate. The present study evaluated the question of whether AA affiliation appears causally related to positive alcohol-related outcomes in a sample of 2,319 male alcohol-dependent patients. An initial structural equation model indicated that 1-year posttreatment levels of AA affiliation predicted lower alcohol-related problems at 2-year follow-up, whereas level of alcohol-related problems at 1-year did not predict AA affiliation at 2-year follow-up. Additional models found that these effects were not attributable to motivation or psychopathology. The findings are consistent with the hypothesis that AA participation has a positive effect on alcohol-related outcomes.
Gulamhusein, Aliya F.; Juran, Brian D.
Genome wide association studies (GWAS) have been a significant technological advance in our ability to evaluate the genetic architecture of complex diseases such as Primary Biliary Cirrhosis (PBC). To date, six large-scale studies have been performed which identified 27 non-HLA risk loci associated with PBC. The identified risk variants emphasize important disease concepts; namely, that disturbances in immunoregulatory pathways are important in the pathogenesis of PBC and that such perturbations are shared among a diverse number of autoimmune diseases – suggesting the risk architecture may confer a generalized propensity to autoimmunity not necessarily specific to PBC. Furthermore, the impact of non-HLA risk variants, particularly in genes involved with IL-12 signaling, and ethnic variation in conferring susceptibility to PBC have been highlighted. While GWAS have been a critical stepping-stone in understanding common genetic variation contributing to PBC, limitations pertaining to power, sample availability, and strong linkage disequilibrium across genes have left us with an incomplete understanding of the genetic underpinnings of disease pathogenesis. Future efforts to gain insight into this missing heritability, the genetic variation that contributes to important disease outcomes and the functional consequences of associated variants will be critical if practical clinical translation is to be realized. PMID:26676814
Caetano, Raul; Vaeth, Patrice A C; Rodriguez, Lori A
OBJECTIVE: To examine the association between acculturation, birthplace, and alcohol-related social problems across Hispanic national groups. METHOD: 5,224 Hispanic adults (18+ years) were interviewed using a multistage cluster sample design in Miami, New York, Philadelphia, Houston, and Los Angeles. RESULTS: Multivariate analysis shows no association between acculturation and problems among men or women. Birthplace is a risk factor for social problems among both genders. Among men, Mexican Americans, Puerto Ricans, and South/Central Americans are more likely to report social problems than Cuban Americans. Other risk factors for men are unemployment, a higher volume of drinking, and a higher frequency of binge drinking. Among women, Mexican American origin and binge drinking are also risk factors for reporting problems. CONCLUSIONS: U.S.-born Hispanics may experience stress and other detrimental effects to health because of their minority status, which may increase the likelihood of more drinking and the development of alcohol-related problems.
Giancola, Peter R.; Josephs, Robert A.; DeWall, C. Nathan; Gunn, Rachel L.
The primary purpose of this article is to apply the attention allocation model (AAM; Steele & Josephs, 1990) to the explanation, as well as the prevention, of alcohol-related violence. The AAM contends that alcohol has a “myopic” effect on attentional capacity that presumably facilitates aggression by narrowing attentional focus on the most salient provocative cues, that are naturally present in hostile situations, rather than less salient inhibitory cues. Data are presented to demonstrate support for the AAM with regard to alcohol-related aggression. The model has also been expanded to suggest some intermediary mechanisms that may account for how distracting attention away from provocative cues might be involved in the reduction of aggression. Finally, a number of practical suggestions are put forth regarding how the AAM can be applied to the prevention of intoxicated aggression. PMID:19938917
Giancola, Peter R; Josephs, Robert A; DeWall, C Nathan; Gunn, Rachel L
The primary purpose of this article is to apply the attention-allocation model (AAM; Steele and Josephs, 1990 ) to the explanation, as well as the prevention, of alcohol-related violence. The AAM contends that alcohol has a "myopic" effect on attentional capacity that presumably facilitates aggression by narrowing attentional focus on the most salient provocative cues that are naturally present in hostile situations, rather than on less salient inhibitory cues. Data are presented to demonstrate support for the AAM with regard to alcohol-related aggression. The model has also been expanded to suggest some intermediary mechanisms that may account for how distracting attention away from provocative cues might be involved in the reduction of aggression. Finally, a number of practical suggestions are put forth regarding how the AAM can be applied to the prevention of intoxicated aggression.
Gauffin, Karl; Hjern, Anders; Vinnerljung, Bo; Björkenstam, Emma
The aim of this paper is to estimate the cumulative effect of childhood household dysfunction (CHD) on alcohol related illness and death later in life and to test the interaction between CHD and socioeconomic background. The study utilised Swedish national registers including data of a Swedish national cohort born 1973-82 (n = 872,912), which was followed from age 18 to 29-40 years. Cox regression analyses were used to calculate hazard ratios (HR) for alcohol related illness or death in young adulthood. The CHD measure consisted of seven indicators: parental alcohol/drug misuse, mental health problems, criminality, death, divorce, social assistance, and child welfare interventions. Childhood socioeconomic position (SEP) was indicated by parental occupational status. Outcomes were alcohol related inpatient hospital care, specialised outpatient care or deaths. Using the highest socioeconomic group without CHD experience as a reference, those in the same socioeconomic group with one indicator of CHD had HRs of 2.1 [95% CI: 1.7-2.5], two CHD indicators 5.6 [4.4-7.1], three or more indicators 9.4 [7.1-12.4] for retrieving inpatient care. Socioeconomic disadvantage further increased the risks-those with low socioeconomic background and three CHD indicators or more had a HR of 12.5 [10.9-14.3]. Testing for interaction suggests that the combined HRs deviates from additivity [Synergy index: 1.6, 95% CI: 1.4-1.9]. The results for outpatient care were similar, but not as pronounced. In conclusion, this Swedish national cohort study shows that childhood household dysfunction is strongly and cumulatively associated to alcohol related illness later in life and that it interacts with socioeconomic disadvantage.
Shy, Bradley D; Hoffman, Robert S
Although alcohol use has long been a significant cause of hospital presentations, little is published regarding the long-term demographic changes that have occurred at a single hospital site. To address this deficit, we prospectively studied all acute alcohol-related presentations to Bellevue Hospital Center (New York, NY) and compared this contemporary data set with one from the same institution from 1902 to 1935. We prospectively identified all patients presenting to the emergency department because of acute alcohol use over an 8-week period in 2009. We described the basic attributes of patients presenting currently because of alcohol and compared these data to those previously described between 1902 and 1935. We also compared our census data with contemporaneous data from all patients presenting to this hospital site. During the study period, 560 patients presented because of acute alcohol use which extrapolated to an estimated 3,800 patients over the calendar year. This compares to 7,600 presentations recorded annually early in the twentieth century. Twelve percent of patients in 2009 were female as compared to 18 % of patients between 1934 and 1935. Patients with alcohol-related presentations in 2009 were more likely to be admitted than contemporaneous patients without an alcohol-related presentation (30 vs. 19 % admitted; p < 0.001). Since first measured 110 years ago at one large New York City hospital, alcohol-related presentations remain common representing 5 % of all emergency department visits. This demonstrates alcoholism's continuing toll on society's limited medical resources and on public health as a whole.
Gauffin, Karl; Hjern, Anders; Vinnerljung, Bo; Björkenstam, Emma
The aim of this paper is to estimate the cumulative effect of childhood household dysfunction (CHD) on alcohol related illness and death later in life and to test the interaction between CHD and socioeconomic background. The study utilised Swedish national registers including data of a Swedish national cohort born 1973–82 (n = 872 912), which was followed from age 18 to 29–40 years. Cox regression analyses were used to calculate hazard ratios (HR) for alcohol related illness or death in young adulthood. The CHD measure consisted of seven indicators: parental alcohol/drug misuse, mental health problems, criminality, death, divorce, social assistance, and child welfare interventions. Childhood socioeconomic position (SEP) was indicated by parental occupational status. Outcomes were alcohol related inpatient hospital care, specialised outpatient care or deaths. Using the highest socioeconomic group without CHD experience as a reference, those in the same socioeconomic group with one indicator of CHD had HRs of 2.1 [95% CI: 1.7–2.5], two CHD indicators 5.6 [4.4–7.1], three or more indicators 9.4 [7.1–12.4] for retrieving inpatient care. Socioeconomic disadvantage further increased the risks–those with low socioeconomic background and three CHD indicators or more had a HR of 12.5 [10.9–14.3]. Testing for interaction suggests that the combined HRs deviates from additivity [Synergy index: 1.6, 95% CI: 1.4–1.9]. The results for outpatient care were similar, but not as pronounced. In conclusion, this Swedish national cohort study shows that childhood household dysfunction is strongly and cumulatively associated to alcohol related illness later in life and that it interacts with socioeconomic disadvantage. PMID:26991657
Chachamovich, Eduardo; Ding, Yang; Turecki, Gustavo
Suicide is one of the major causes of deaths worldwide. Several studies have showed that alcohol use disorders (AUD) are associated with suicide ideation, suicide attempts, and suicide completion. The majority of the theoretical conceptualization and the bulk of evidence on suicidal behavior and AUD are based on investigations of nonfatal cases because data on nonfatal suicidal behaviors are more readily available. This study aims to explore demographic, clinical, and behavioral dimensions in a large sample of alcohol-related suicides compared to an age-gender matched sample of non-AUD suicides to identify specific factors associated with AUD suicides. We conducted a psychological autopsy study with 158 pairs of AUD and non-AUD suicides. Findings showed that AUD suicides have lower educational level, more biological children and were more likely to be heavy smokers (OR=3.32). Cases were more likely to have family history of alcohol (OR=1.73) and drug abuse (OR=3.61). Subjects had similar prevalences of depressive disorders, anxiety disorders or psychotic disorders. AUD suicides were more likely to meet criteria for current cocaine abuse/dependence (OR=6.64). With respect to personality disorders, AUD suicides presented higher prevalence of Antisocial Personality Disorder (OR=4.68), and were less likely to meet criteria for Avoidant (OR=0.26) and Obsessive-Compulsive Personality Disorders (OR=0.35). Impulsivity scores were higher in AUD suicides (p=0.18), as well as aggression scores (p<0.001). Results form the conditional logistic regression models showed that cocaine abuse/dependence (OR=4.20) and Antisocial Personality Disorder (OR=6.24) were associated with AUD suicide. After controlling for impulsive-aggressive behaviors, levels of aggression were the only psychopathological feature statistically different between AUD and non-AUD suicides (OR=1.28). In conclusion, higher levels of aggressive behaviors are a specific characteristic of AUD suicides. Apart from
Dvorak, Robert D; Kramer, Matthew P; Stevenson, Brittany L; Sargent, Emily M; Kilwein, Tess M
Spring break (SB) can lead to heavy episodic drinking and increased alcohol-related risks. This may be especially relevant for women. The current study utilized deviance regulation theory to increase the use of protective behavioral strategies (PBSs) among female college students on SB. Female college students going on SB (n = 62) completed a screening, a pre-SB intervention (where they were randomly assigned to receive either a positively or negatively framed message about individuals who do or do not use PBS), and a post-SB assessment that provided alcohol and PBS use data for each day of SB (n = 620 person-days). Data were analyzed using a multilevel structural equation model. In the negative frame, SB PBS use was higher among those who perceived SB PBS norms to be more common on SB relative to non-SB. In the positive frame, SB PBS use was higher among those who perceived SB PBS norms to be less common on SB relative to non-SB. These associations did not result in lower alcohol consumption, but did result in a lower likelihood of experiencing alcohol-related problems during SB. These results suggest that a brief online intervention, that utilizes targeted messages based on normative perceptions of SB PBS use, could be an effective strategy for reducing alcohol-related consequences among college student women during SB. (PsycINFO Database Record
Martineau, F.P.; Graff, H.; Mitchell, C.; Lock, K.
Background The power to influence many social determinants of health lies within local government sectors that are outside public health's traditional remit. We analyse the challenges of achieving health gains through local government alcohol control policies, where legal and professional practice frameworks appear to conflict with public health action. Methods Current legislation governing local alcohol control in England and Wales is reviewed and analysed for barriers and opportunities to implement effective population-level health interventions. Case studies of local government alcohol control practices are described. Results Addressing alcohol-related health harms is constrained by the absence of a specific legal health licensing objective and differences between public health and legal assessments of the relevance of health evidence to a specific place. Local governments can, however, implement health-relevant policies by developing local evidence for alcohol-related health harms; addressing cumulative impact in licensing policy statements and through other non-legislative approaches such as health and non-health sector partnerships. Innovative local initiatives—for example, minimum unit pricing licensing conditions—can serve as test cases for wider national implementation. Conclusions By combining the powers available to the many local government sectors involved in alcohol control, alcohol-related health and social harms can be tackled through existing local mechanisms. PMID:23933915
Hingson, R; Zakocs, R; Heeren, T; Winter, M; Rosenbloom, D; DeJong, W
Objective: This analysis tested whether comprehensive community interventions that focus on reducing alcohol availability and increasing substance abuse treatment can reduce alcohol related fatal traffic crashes. Intervention: Five of 14 communities awarded Fighting Back grants by The Robert Wood Johnson Foundation to reduce substance abuse and related problems attempted to reduce availability of alcohol and expand substance abuse treatment programs (FBAT communities). Program implementation began on 1 January 1992. Design: A quasi-experimental design matched each program community to two or three other communities of similar demographic composition in the same state. Main outcome measures: The ratio of fatal crashes involving a driver or pedestrian with a blood alcohol concentration of 0.01% or higher, 0.08% or higher, or 0.15% or higher were examined relative to fatal crashes where no alcohol was involved for 10 years preceding and 10 years following program initiation. Results: Relative to their comparison communities, the five FBAT communities experienced significant declines of 22% in alcohol related fatal crashes at 0.01% BAC or higher, 20% at 0.08% or higher, and 17% at 0.15% or higher relative to fatal crashes not involving alcohol. Conclusions: Community interventions to reduce alcohol availability and increase substance abuse treatment can reduce alcohol related fatal traffic crashes. PMID:15805436
Taylor, Jennifer E; Haddock, Keith; Poston, W S Carlos; Talcott, Wayne G
The negative impact of alcohol use on workplace performance is of significant concern to the U.S. military, given the costs associated with recruiting, hiring, and training personnel. However, little is known about the extent of potential alcohol use problems of recruits. We examined the history of alcohol-related problems among recruits entering the Air Force (N=37858). Although the average age of recruits was <21 years, 78% reported consuming alcohol and 49% reported binging before basic military training. Recruits who drank reported having negative alcohol-related outcomes (NAROs). In fact, >95% reported that they or someone else had been injured as a result of their drinking and that a relative, friend, doctor, or other health care worker has been concerned about their drinking. The remaining NAROs were reported by approximately one-quarter of those who drank. However, recruits who reported binge drinking were substantially more likely to report more NAROs, such as morning drinking, inability to stop drinking, having others be concerned about their drinking, having blackouts, fighting, having injured or been injured, feeling guilty about their drinking, and wanting to reduce the amount they drink. Results suggest that alcohol-related problems are common among recruits before basic military training and screening for future problems may be beneficial.
Dennhardt, Ashley A; Murphy, James G
Although levels of heavy drinking and alcohol-related problems are high in college students, there is significant variability in the number and type of problems experienced, even among students who drink heavily. African American students drink less and experience fewer alcohol-related problems than European American students, but are still at risk, and little research has investigated the potentially unique patterns and predictors of problems among these students. Depression, distress tolerance, and delay discounting have been implicated in adult substance abuse and may be important predictors of alcohol problem severity among college students. We examined the relationship between these variables and alcohol-related problems among African American and European American students (N = 206; 53% female; 68% European American; 28% African American) who reported recent heavy drinking. In regression models that controlled for drinking level, depression, distress tolerance, and delay discounting were associated with alcohol problems among African American students, but only depression was associated with alcohol problems among European American students. These results suggest that negative affect is a key risk factor for alcohol problems among college student drinkers. For African American students, the inability to tolerate negative emotions and to organize their behavior around future outcomes may also be especially relevant risk factors.
Marcellin, P; de Bony, F; Garret, C; Altman, C; Boige, V; Castelnau, C; Laurent-Puig, P; Trinchet, J C; Rolan, P; Chen, C; Mamet, J P; Bidault, R
Aims Lamotrigine, an antiepileptic drug, is cleared from the systemic circulation mainly by glucuronidation. The possibility of changes in the pharmacokinetics of lamotrigine in plasma owing to hepatic dysfunction has been evaluated. Methods Thirty-six subjects, including 24 patients with various degrees of liver cirrhosis and 12 healthy volunteers received a single 100 mg dose of lamotrgine. Blood samples were taken for 7 days in all subjects, except nine with severe cirrhosis, who had a 29 day blood sampling period. Results The pharmacokinetics of lamotrigine were comparable between the patients with moderate cirrhosis (corresponding to Child-Pugh grade A) and the healthy subjects. Plasma oral clearance mean ratios (90% confidence interval) in patients with severe cirrhosis without or with ascites (corresponding, respectively, to Child-Pugh grade B and C) to healthy subjects were, respectively, 60% (44%, 83%) and 36% (25%, 52%). Plasma half-life mean ratios (90% confidence interval) in these two patient groups to healthy subjects were, respectively, 204% (149%, 278%) and 287% (202%, 408%). Conclusions Lamotrigine administered as a single oral dose of 100 mg was well tolerated in all groups. Initial, escalation and maintenance doses should generally be reduced by approximately 50 or 75% in patients with Child-Pugh Grade B or C cirrhosis. Escalation and maintenance doses should be adjusted according to clinical response. PMID:11421997
Hackl, Christina; Schlitt, Hans J; Renner, Philipp; Lang, Sven A
The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary or metastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis.
Hackl, Christina; Schlitt, Hans J; Renner, Philipp; Lang, Sven A
The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary or metastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis. PMID:26973411
Fede, Giuseppe; Privitera, Graziella; Tomaselli, Tania; Spadaro, Luisa; Purrello, Francesco
Hyperdynamic syndrome is a well-known clinical condition found in patients with cirrhosis and portal hypertension, characterized by increased heart rate and cardiac output, and reduced systemic vascular resistance and arterial blood pressure. The leading cause of hyperdynamic circulation in cirrhotic patients is peripheral and splanchnic vasodilatation, due to an increased production/activity of vasodilator factors and decreased vascular reactivity to vasoconstrictors. The term “cirrhotic cardiomyopathy” describes impaired contractile responsiveness to stress, diastolic dysfunction and electrophysiological abnormalities in patients with cirrhosis without known cardiac disease. Underlying circulatory and cardiac dysfunctions are the main determinant in the development of hepatorenal syndrome in advanced cirrhosis. Moreover, the clinical consequences of cirrhosis-related cardiovascular dysfunction are evident during and after liver transplantation, and after transjugular intrahepatic portosystemic shunt insertion. Cardiovascular complications following these procedures are common, with pulmonary edema being the most common complication. Other complications include overt heart failure, arrhythmia, pulmonary hypertension, pericardial effusion, and cardiac thrombus formation. This review discusses the circulatory and cardiovascular dysfunctions in cirrhosis, examining the pathophysiologic and clinical implications in light of the most recent published literature. PMID:25608575
Leonardi, Filippo; Maria, Nicola De; Villa, Erica
The liver plays a crucial role in coagulation cascade. Global hemostatic process is profoundly influenced by the presence of liver disease and its complications. Patients with cirrhosis have impaired synthesis of most of the factors involved in coagulation and fibrinolysis process due to a reduced liver function and altered platelet count secondary to portal hypertension. Altered routine tests and thrombocytopenia were considered in the past as associated with increased risk of bleeding. These concepts explain both the routine use of plasma and/or platelets transfusion in patients with liver cirrhosis, especially before invasive procedures, and why these patients were considered “auto-anticoagulated”. New recent evidences show that patients with liver cirrhosis have a more complex hemostatic alteration. Despite the presence of altered levels of factors involved in primary hemostasis, coagulation and fibrinolysis, patients with stable cirrhosis have a rebalanced hemostatic, which however can easily be altered by decompensation or infection, both in hemorrhagic or thrombotic direction. Patients with cirrhosis have an increased risk of venous thrombotic events (namely portal vein thrombosis) while bleeding seems to be related to the grade of portal hypertension rather than to a hemostatic imbalance. The use of anticoagulants both as treatment or prophylaxis is safe, reduces the rate of portal vein thrombosis and decompensation, and improves survival. Standard laboratory coagulation tests are unable to predict bleeding and are inadequate for the assessment of hemostatic status in these patients, hence more comprehensive tests are required to guide the management of thrombotic and bleeding complications. PMID:28288507
Coulter, Robert W.S.; Blosnich, John R.; Bukowski, Leigh A.; Herrick, A. L.; Siconolfi, Daniel E.; Stall, Ron D.
Background Little is known about differences in alcohol use and alcohol-related problems between transgender- and nontransgender-identified populations. Using data from a large-scale health survey, we compare the drinking patterns and prevalence of alcohol-related problems of transgender-identified individuals to nontransgender-identified males and females. For transgender-identified people, we examine how various forms of victimization relate to heavy episodic drinking (HED). Methods Cross-sectional surveys were completed by 75,192 students aged 18–29 years attending 120 post-secondary educational institutions in the United States from 2011–2013. Self-reported measures included alcohol use, alcohol-related problems, victimization, and sociodemographics, including 3 gender-identity groups: transgender-identified individuals; nontransgender-identified males; and nontransgender-identified females. Results Compared to transgender-identified individuals, nontransgender-identified males were more likely to report HED in the past 2 weeks (relative risk=1.42; p=0.006); however, nontransgender-identified males and females reported HED on fewer days than transgender-identified people (incidence-rate ratios [IRRs] ranged from 0.28–0.43; p-values<0.001). Compared to transgender-identified people, nontransgender-identified males and females had lower odds of past-year alcohol-related sexual assault and suicidal ideation (odds ratios ranged from 0.24–0.45; p-values<0.05). Among transgender-identified people, individuals who were sexually assaulted (IRR=3.21, p=0.011) or verbally threatened (IRR=2.42, p=0.021) in the past year had greater HED days than those who did not experience those forms of victimization. Conclusions Compared to transgender-identified people, nontransgender-identified males and females: have fewer HED occasions (despite nontransgender-identified males having greater prevalence of HED); and are at lower risk for alcohol-related sexual assaults and
Rivera Irigoin, Robin; Abilés, Jimena
Given the liver's multiple synthetic, regulatory and detoxifying functions, one of the characteristics accompanying severe hepatocellular dysfunction is the presence of malnutrition. This disorder is highly frequent in liver cirrhosis, even in the relatively early stages of the disease. Independently of the cause of the cirrhosis, poor nutritional status is associated with a worse prognosis and therefore early intervention to correct nutrient deficiency can prolong life expectancy, improve quality of life, reduce complications and increase the probability of successful transplantation. The present article reviews current knowledge of the diagnosis and management of malnutrition in patients with cirrhosis. Special attention is paid to the concept of the late evening snack and its characteristics, composition and probable benefits in the course of the disease.
Gao, Jun; Qiao, Liang; Wang, Bingyuan
Primary biliary cirrhosis (PBC) is a chronic progressive autoimmune cholestatic liver disease characterized by highly specific antimitochondrial antibodies (AMAs) and the specific immune-mediated injury of small intrahepatic bile ducts. Unique apoptotic feature of biliary epithelial cells (BECs) may contribute to apotope presentation to the immune system, causing unique tissue damage in PBC. Perpetuation of inflammation may result in senescence of BECs, contributing to irreversible loss of bile duct. In addition to the classic liver manifestations, focal inflammation and tissue damage are also seen in salivary glands and urinary tract in a significant proportion of PBC patients. These findings provide potent support to the idea that molecular mimicry may be involved in the breakdown of autoimmune tolerance and mucosal immunity may lead to a systematic epithelitis in PBC patients. Thus, PBC is considered a generalized epithelitis in clinical practice. PMID:25803105
Iglesias, Verónica; Rico, Lucia; Ortega, Alicia; Muñoz-Conejero, Eva; García-Pajares, Felix; Bermejo-Martin, Jesus F.
The role of systemic immunity in the pathogenesis of cirrhosis is not fully understood. Analysis of transcriptomic profiles in blood is an easy approach to obtain a wide picture of immune response at the systemic level. We studied gene expression profiles in blood from thirty cirrhotic patients and compared them against those of eight healthy volunteers. Most of our patients were male [n = 21, 70%] in their middle ages [57.4 ± 6.8 yr]. Alcohol abuse was the most frequent cause of cirrhosis (n = 22, 73%). Eleven patients had hepatocellular carcinoma (36.7%). Eight patients suffered from hepatitis C virus infection (26.7%). We found a signature constituted by 3402 genes which were differentially expressed in patients compared to controls (2802 over-expressed and 600 under-expressed). Evaluation of this signature evidenced the existence of an active pro-fibrotic transcriptomic program in the cirrhotic patients, involving the [extra-cellular matrix (ECM)-receptor interaction] & [TGF-beta signaling] pathways along with the [Cell adhesion molecules] pathway. This program coexists with alterations in pathways participating in [Glycine, serine and threonine metabolism], [Phenylalanine metabolism], [Tyrosine metabolism], [ABC transporters], [Purine metabolism], [Arachidonic acid metabolism]. In consequence, our results evidence the co-existence in blood of a genomic program mediating pro-fibrotic mechanisms and metabolic alterations in advanced cirrhosis. Monitoring expression levels of the genes involved in these programs could be of interest for predicting / monitoring cirrhosis evolution. These genes could constitute therapeutic targets in this disease. PMID:26317806
Kenney, Shannon R.; Napper, Lucy E.; LaBrie, Joseph W.
Background Participation in drinking games is associated with excessive drinking and alcohol risks. Despite the growing literature documenting the ubiquity and consequences of drinking games, limited research has examined the influence of psychosocial factors on the experience of negative consequences as the result of drinking game participation. Objectives The current event-level study examined the relationships among drinking game participation, social anxiety, drinking refusal self-efficacy (DRSE) and alcohol-related consequences in a sample of college students. Methods Participants (n =976) reported on their most recent drinking occasion in the past month in which they did not preparty. Results After controlling for sex, age, and typical drinking, higher levels of social anxiety, lower levels of DRSE, and playing drinking games predicted greater alcohol-related consequences. Moreover, two-way interactions (Social Anxiety × Drinking Games, DRSE × Drinking Games) demonstrated that social anxiety and DRSE each moderated the relationship between drinking game participation and alcohol-related consequences. Participation in drinking games resulted in more alcohol problems for students with high social anxiety, but not low social anxiety. Students with low DRSE experienced high levels of consequences regardless of whether they participated in drinking games; however, drinking game participation was associated with more consequences for students confident in their ability to resist drinking. Conclusion Findings highlight the important role that social anxiety and DRSE play in drinking game-related risk, and hence provide valuable implications for screening at-risk students and designing targeted harm reduction interventions that address social anxiety and drink refusal in the context of drinking games. PMID:25192207
Stanley, N. N.; Ackrill, P.; Wood, J.
Abnormal lung perfusion scans using radioactive particles were found in five out of six cases of hepatic cirrhosis with arterial hypoxaemia. None had clinical evidence of cardiopulmonary disease or signs of pulmonary embolism on arteriography. The scan defects are probably caused by a disorder of the pulmonary microvasculature, which may show regional variation in severity. ImagesFIG. 1FIG. 2 PMID:4645896
Tsimmerman, Ya S
Modern data on primary biliary liver cirrhosis are presented including the definition, prevalence, possible etiological factors, and detailed description of pathogenesis (autoimmune mechanisms, intrahepatic cholestasis, hereditary predisposition, environmental factors) and clinical picture. Also considered are complications and concomitant diseases, methods of laboratory, instrumental and morphological diagnostics, approaches to medicamental treatment and its effectiveness, indications for liver transplantation.
Liberal, Rodrigo; Grant, Charlotte R
Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952
Hummer, Justin F.; Pedersen, Eric. R.; Mirza, Tehniat; LaBrie, Joseph W.
This study contributes to the scarce research on U.S. college students studying abroad by documenting general and sexual negative alcohol-related risks and factors associated with such risk. The manner of drinking (quantity vs. frequency), predeparture expectations surrounding alcohol use while abroad, culture-related social anxiety, and perceived disparity between home and host cultures differentially predicted consequences abroad. The findings include important implications for student affairs professionals in developing study abroad–specific interventions and resources to maintain student well-being while abroad. PMID:23505594
O’Brien, Mary Claire; McNamara, Robert S; McCoy, Thomas P; Sutfin, Erin L; Wolfson, Mark; Rhodes, Scott D
Members of Greek-letter societies are the heaviest drinkers on college campuses, and experience more alcohol-related problems than their peers. This study reports the results of a web-based survey administered to stratified random samples of college students from ten North Carolina universities. Greek-letter status was a significant independent risk factor for increased injury (both experienced and caused to others), even after adjusting for drinking behaviors. Prevention, screening, and intervention strategies are discussed in the context of these results. PMID:22689586
Siqueira, Cíntia; de Moura, Miguel Carneiro; Pedro, Ana Julia; Rocha, Paula
AIM: To evaluate whether serum levels of nitric oxide (NO•) and plasma levels of cyclic guanosine monophosphate (cGMP) and total glutathione (GSH) are altered in patients with alcoholic cirrhosis and to examine their correlation with the severity of liver disease. METHODS: Twenty-six patients with alcoholic liver cirrhosis were studied. Serum levels of NO• and plasma levels of cGMP and GSH were measured in 7 patients with compensated alcoholic cirrhosis (Child-Pugh A) and 19 patients with advanced cirrhosis (Child-Pugh B and C). The model for end-stage liver disease (MELD) score was evaluated. Sixteen healthy volunteers served as controls. Liver enzymes and creatinine levels were also tested. RESULTS: NO• and cGMP levels were higher in patients with Child-Pugh B and C cirrhosis than in Child-Pugh A cirrhosis or controls (NO•: 21.70 ± 8.07 vs 11.70 ± 2.74; 21.70 ± 8.07 vs 7.26 ± 2.47 μmol/L, respectively; P < 0.001) and (cGMP: 20.12 ± 6.62 vs 10.14 ± 2.78; 20.12 ± 6.62 vs 4.95 ± 1.21 pmol/L, respectively; P < 0.001). Total glutathione levels were lower in patients with Child-Pugh B and C cirrhosis than in patients with Child-Pugh A cirrhosis or controls (16.04 ± 6.06 vs 23.01 ± 4.38 or 16.04 ± 6.06 vs 66.57 ± 26.23 μmol/L, respectively; P < 0.001). There was a significant correlation between NO• and cGMP levels in all patients with alcoholic cirrhosis. A significant negative correlation between reduced glutathione/glutathione disulfide and the MELD score was found in all cirrhotic patients. CONCLUSION: Our results suggest a role for oxidative stress in alcoholic liver cirrhosis, which is more significant in decompensated patients with higher levels of NO• and cGMP and lower GSH levels than in compensated and control patients. Altered mediator levels in decompensated patients may influence the hemodynamic changes in and progression of liver disease. PMID:18186561
Bravo, Adrian J; Kelley, Michelle L; Hollis, Brittany F
This study examined how work stressors were associated with sleep quality and alcohol-related problems among U.S. Navy members over the course of deployment. Participants were 101 U.S. Navy members assigned to an Arleigh Burke-class destroyer who experienced an 8-month deployment after Operational Enduring Freedom/Operation Iraqi Freedom. Approximately 6 weeks prior to deployment, 6 weeks after deployment, and 6 months reintegration, participants completed measures that assessed work stressors, sleep quality, and alcohol-related problems. A piecewise latent growth model was conducted in which the structural paths assessed if work stressors influenced sleep quality or its growth over time, and in turn if sleep quality influenced alcohol-related problems intercepts or growth over time. A significant indirect effect was found such that increases in work stressors from pre- to postdeployment predicted decreases in sleep quality, which in turn were associated with increases in alcohol-related problems from pre- to postdeployment. These effects were maintained from postdeployment through the 6-month reintegration. Findings suggest that work stressors may have important implications for sleep quality and alcohol-related problems. Positive methods of addressing stress and techniques to improve sleep quality are needed as both may be associated with alcohol-related problems among current Navy members.
Do predisposing and family background characteristics modify or confound the relationship between drinking frequency and alcohol-related aggression? A study of late adolescent and young adult drinkers.
Wells, Samantha; Graham, Kathryn; Speechley, Mark; Koval, John J
The present study examined whether predisposing and family background characteristics confounded (common cause/general deviance theory) or modified (conditional/interactive theory) the association between drinking frequency and alcohol-related aggression. A secondary analysis of the US National Longitudinal Survey of Youth was conducted using a composite sample of drinkers, ages 17 to 21, from the 1994, 1996, and 1998 Young Adult surveys (n=602). No evidence of confounding of the relationship between drinking frequency and alcohol-related aggression was found. In addition, predisposing characteristics did not modify the association between drinking frequency and alcohol-related aggression. However, family background variables (mother's education and any poverty) were important explanatory variables for alcohol-related aggression among males, whereas recent aggression (fights at school or work) was an important predictor for females. Overall, lack of support for the conditional/interactive and common cause theories of the alcohol and aggression relationship suggests that alcohol has an independent explanatory role in alcohol-related aggression. In addition, the gender differences found in the present study highlight the need for more gender-focussed research on predictors of alcohol-related aggression, especially among adolescents and young adults.
Howell, Steven M; Barry, Adam E; Pitney, William A
Compared with their nonathlete peers, collegiate athletes consume higher quantities of alcohol, drink with greater frequency, and exhibit an increased propensity to engage in heavy episodic drinking (ie, binge drinking), which often may result in alcohol-related consequences. Moreover, collegiate athletes are also more likely to engage in other maladaptive lifestyle behaviors, such as participating in physical fights and riding with an intoxicated driver, and less likely to engage in protective behaviors, such as wearing a helmet while operating a motorcycle, moped, or bicycle. Taken together, these behaviors clearly pose a health risk for student-athletes and increase the likelihood that they will experience an alcohol-related unintentional injury (ARUI). An ARUI represents a risk not only to the health and well-being of collegiate athletes but also to their athletic performances, collegiate careers, and potential professional opportunities. Therefore, athletic trainers need to be equipped with the knowledge and skills to provide face-to-face brief interventions to student-athletes presenting with ARUIs and to evaluate the effect of their involvement. We address potential action items for implementation by athletic trainers.
Howell, Steven M.; Barry, Adam E.; Pitney, William A.
Compared with their nonathlete peers, collegiate athletes consume higher quantities of alcohol, drink with greater frequency, and exhibit an increased propensity to engage in heavy episodic drinking (ie, binge drinking), which often may result in alcohol-related consequences. Moreover, collegiate athletes are also more likely to engage in other maladaptive lifestyle behaviors, such as participating in physical fights and riding with an intoxicated driver, and less likely to engage in protective behaviors, such as wearing a helmet while operating a motorcycle, moped, or bicycle. Taken together, these behaviors clearly pose a health risk for student-athletes and increase the likelihood that they will experience an alcohol-related unintentional injury (ARUI). An ARUI represents a risk not only to the health and well-being of collegiate athletes but also to their athletic performances, collegiate careers, and potential professional opportunities. Therefore, athletic trainers need to be equipped with the knowledge and skills to provide face-to-face brief interventions to student-athletes presenting with ARUIs and to evaluate the effect of their involvement. We address potential action items for implementation by athletic trainers. PMID:26287493
Wintemute, Garen J
Alcohol use and firearm ownership are risk factors for violent injury and death. To determine whether firearm ownership and specific firearm-related behaviours are associated with alcohol-related risk behaviours, the author conducted a cross-sectional study using Behavioral Risk Factor Surveillance System data for eight states in the USA from 1996 to 1997 (the most recent data available). Altogether, 15 474 respondents provided information on firearm exposure. After adjustment for demographics and state of residence, firearm owners were more likely than those with no firearms at home to have ≥5 drinks on one occasion (OR 1.32; 95% CI 1.16 to 1.50), to drink and drive (OR 1.79; 95% CI 1.34 to 2.39) and to have ≥60 drinks per month (OR 1.45; 95% CI 1.14 to 1.83). Heavy alcohol use was most common among firearm owners who also engaged in behaviours such as carrying a firearm for protection against other people and keeping a firearm at home that was both loaded and not locked away. The author concludes that firearm ownership and specific firearm-related behaviours are associated with alcohol-related risk behaviours.
Purvis, Danielle M; Gallagher, Kathryn E; Parrott, Dominic J
Alcohol Myopia Theory (AMT; Steele & Josephs, 1990) purports that alcohol facilitates aggression by narrowing attentional focus onto salient and instigatory cues common to conflict situations. However, few tests of its counterintuitive prediction - that alcohol may decrease aggression when inhibitory cues are most salient - have been conducted. The present study examined whether an AMT-inspired self-awareness intervention manipulation would reduce heavy drinking men's intoxicated aggression toward women and also examined whether a relevant individual variable, locus of control, would moderate this effect. Participants were 102 intoxicated male heavy drinkers who completed a self-report measure of locus of control and completed the Taylor Aggression Paradigm (Taylor, 1967). In this task, participants administered electric shocks to, and received electric shocks from, a fictitious female opponent while exposed to an environment saturated with or devoid of self-awareness cues. Results indicated that the self-awareness manipulation was associated with less alcohol-related aggression toward the female confederate for men who reported an internal, but not an external, locus of control. Findings support AMT as a theoretical framework to inform preventative interventions for alcohol-related aggression and highlight the importance of individual differences in receptivity to such interventions.
Walvoort, Serge JW; van der Heijden, Paul T; Kessels, Roy PC; Egger, Jos IM
Aim Impaired illness insight may hamper treatment outcome in patients with alcohol-related cognitive deficits. In this study, a short questionnaire for the assessment of illness insight (eg, the Q8) was investigated in patients with Korsakoff’s syndrome (KS) and in alcohol use disorder (AUD) patients with mild neurocognitive deficits. Methods First, reliability coefficients were computed and internal structure was investigated. Then, comparisons were made between patients with KS and patients with AUD. Furthermore, correlations with the Dysexecutive Questionnaire (DEX) were investigated. Finally, Q8 total scores were correlated with neuropsychological tests for processing speed, memory, and executive function. Results Internal consistency of the Q8 was acceptable (ie, Cronbach’s α =0.73). The Q8 items represent one factor, and scores differ significantly between AUD and KS patients. The Q8 total score, related to the DEX discrepancy score and scores on neuropsychological tests as was hypothesized, indicates that a higher degree of illness insight is associated with a higher level of cognitive functioning. Conclusion The Q8 is a short, valid, and easy-to-administer questionnaire to reliably assess illness insight in patients with moderate-to-severe alcohol-related cognitive dysfunction. PMID:27445476
Sansoè, Giovanni; Aragno, Manuela; Mastrocola, Raffaella; Mengozzi, Giulio; Novo, Erica; Parola, Maurizio
Background Tissue Angiotensin II (Ang-II), produced through local non ACE-dependent pathways, stimulates liver fibrogenesis, renal vasoconstriction and sodium retention. Aim To highlight chymase-dependent pathway of Ang-II production in liver and kidney during cirrhosis development. Methods Liver histology, portal pressure, liver and kidney function, and hormonal status were investigated in rat liver cirrhosis induced through 13 weeks of CCl4, with or without chymase inhibitor SF2809E, administered between 4th and 13th CCl4 weeks; liver and kidney chymase immunolocation and Ang-II content were assessed. Chymase immunohistochemistry was also assessed in normal and cirrhotic human liver, and chymase mRNA transcripts were measured in human HepG2 cells and activated hepatic stellate cells (HSC/MFs) in vitro. Results Rats receiving both CCl4 and SF2809E showed liver fibrotic septa focally linking portal tracts but no cirrhosis, as compared to ascitic cirrhotic rats receiving CCl4. SF2809E reduced portal pressure, plasma bilirubin, tissue content of Ang-II, plasma renin activity, norepinephrine and vasopressin, and increased glomerular filtration rate, water clearance, urinary sodium excretion. Chymase tissue content was increased and detected in α-SMA-positive liver myofibroblasts and in kidney tubular cells of cirrhotic rats. In human cirrhosis, chymase was located in hepatocytes of regenerative nodules. Human HepG2 cells and HSC/MFs responded to TGF-β1 by up-regulating chymase mRNA transcription. Conclusions Chymase, through synthesis of Ang-II and other mediators, plays a role in the derangement of liver and kidney function in chronic liver diseases. In human cirrhosis, chymase is well-represented and apt to become a future target of pharmacological treatment. PMID:27637026
Lin, Ji; Wu, Jian-Feng; Zhang, Qi; Zhang, Hong-Wei; Cao, Guang-Wen
Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8(+) T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.
Westgate, Erin C; Neighbors, Clayton; Heppner, Hannes; Jahn, Susanna; Lindgren, Kristen P
Objective: This study investigated whether self-reports of alcohol-related postings on Facebook by oneself or one’s Facebook friends were related to common motives for drinking and were uniquely predictive of self-reported alcohol outcomes (alcohol consumption, problems, and cravings). Method: Pacific Northwest undergraduates completed a survey of alcohol outcomes, drinking motives, and alcoholrelated Facebook postings. Participants completed the survey online as part of a larger study on alcohol use and cognitive associations. Participants were randomly selected through the university registrar’s office and consisted of 1,106 undergraduates (449 men, 654 women, 2 transgender, 1 declined to answer) between the ages of 18 and 25 years (M = 20.40, SD = 1.60) at a large university in the Pacific Northwest. Seven participants were excluded from analyses because of missing or suspect data. Results: Alcohol-related postings on Facebook were significantly correlated with social, enhancement, conformity, and coping motives for drinking (all ps < .001). After drinking motives were controlled for, self–alcohol-related postings independently and positively predicted the number of drinks per week, alcohol-related problems, risk of alcohol use disorders, and alcohol cravings (all ps < .001). In contrast, friends’ alcohol-related postings only predicted the risk of alcohol use disorders (p < .05) and marginally predicted alcohol-related problems (p = .07). Conclusions: Posting alcohol-related content on social media platforms such as Facebook is associated with common motivations for drinking and is, in itself, a strong predictive indicator of drinking outcomes independent of drinking motives. Moreover, self-related posting activity appears to be more predictive than Facebook friends’ activity. These findings suggest that social media platforms may be a useful target for future preventative and intervention efforts. PMID:24766750
Ali, Ahmad H; Carey, Elizabeth J; Lindor, Keith D
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized histologically by destruction of intrahepatic bile ducts and serologically by the presence of antimitochondrial antibodies. The incidence and prevalence of PBC are increasing. Fatigue and pruritus are common symptoms in PBC, although the proportion of asymptomatic PBC is increasing due to the widespread use of screening biochemical tests and antimitochondrial antibody assays. PBC may eventually lead to cirrhosis and its consequent complications. In the 1980s, PBC was the leading indication for liver transplantation. Ursodeoxycholic acid is the only US FDA-approved therapeutic agent for PBC. Clinical trials have shown that the use of ursodeoxycholic acid in PBC results in reduction of liver biochemistries, a delay in histological progression, a delay in the development of varices and improvement in survival without liver transplantation.
The liver is an important organ with specific functions that influence directly on the nutritional and physiological status of every person. At the presence of any illness or injury in this organ, liver cirrhosis is always its final phase. In this pathology, patients present carbohydrate utilization and storage diminishment, as well as protein and fat catabolism increase. This situation, plus a low ingest and a bad nutrient absorption, results in a high prevalence of malnutrition. Many studies prove the importance of an opportune nutritional treatment in these patients, bringing general benefits and improving their quality of life. It's important to considerate the possible nutritional risks and deficiencies that could appear in the course of the cirrhosis to take opportune actions. The nutritional assessment and treatment is transcendental both in compensated phase (without complications) and in decompensated phase (with complications) of the illness.
Bank, E.R.; Thrall, J.H.; Dantzker, D.R.
The association of hepatic cirrhosis and severe arterial hypoxemia has been well described. Although alterations in ventilatory function may partially account for the hypoxemia, the principal mechanism is thought to be a microangiopathic change in the pulmonary arteriovenous shunting with resultant systemic desaturation. Whole-body radionuclide scans with technetium-99m macroaggrregated albumin (/sup 99m/Tc MAA) labeling have been diagnostic of right-to-left shunting by their demonstration of tracer accumulation within the extrapulmonary circulation. A case of severe pulmonary arteriovenous shunting in an alcoholic patient in whom hepatic disease had not been of apparent clinical significance before radionuclide scanning is reported. He did not have cutaneous angiomata as have all other patients with alcoholic cirrhosis and hypoxemia.
Bank, E.R.; Thrall, J.H.; Dantzker, D.R.
The association of hepatic cirrhosis and severe arterial hypoxemia has been well described. Although alterations in ventilatory function may partially account for the hypoxemia, the principal mechanism is thought to be a microangiopathic change in the pulmonary vasculature resulting in intrapulmonary arteriovenous shunting with resultant systemic desaturation. Whole-body radionuclide scans with technetium-99m macroaggregated albumin labeling have been diagnostic of right-to-left shunting by their demonstration of tracer accumulation within the extrapulmonary circulation. A case of severe pulmonary arteriovenous shunting in an alcoholic patient in whom hepatic disease had not been of apparent clinical significance before radionuclide scanning is reported. He did not have cuntaeous angiomata as have all other patients with alcoholic cirrhosis and hypoxemia.
Imam, Mohamad H; Lindor, Keith D
Our understanding of the natural history of primary biliary cirrhosis (PBC) has been evolving especially following the introduction of ursodeoxycholic acid (UDCA). A clearer understanding of disease pathophysiology and earlier diagnosis with increased prevalence of the disease worldwide has led to increased interest and improved outcomes in patients with PBC. In this article, the authors touch briefly on features of the disease and describe the natural history of PBC prior to and after the introduction of UDCA.
Lammers, Willem J; Kowdley, Kris V; van Buuren, Henk R
Primary biliary cirrhosis (PBC) is a slowly progressive autoimmune liver disease that may ultimately result in liver failure and premature death. Predicting outcome is of key importance in clinical management and an essential requirement for patients counselling and timing of diagnostic and therapeutic interventions. The following factors are associated with progressive disease and worse outcome: young age at diagnosis, male gender, histological presence of cirrhosis, accelerated marked uctopenia in relation to the amount of fibrosis, high serum bilirubin, low serum albumin levels, high serum alkaline phosphatase levels, esophageal varices, hepatocellular carcinoma (HCC) and lack of biochemical response to ursodeoxycholic acid (UDCA). The prognostic significance of symptoms at diagnosis is uncertain. UDCA therapy and liver transplantation have a significant beneficial effect on the outcome of the disease. The Mayo risk score in PBC can be used for estimating individual prognosis. The Newcastle Varices in PBC Score may be a useful clinical tool to predict the risk for development of esophageal varices. Male gender, cirrhosis and non-response to UDCA therapy in particular, are risk factors for development of HCC.
Grüngreiff, Kurt; Reinhold, Dirk; Wedemeyer, Heiner
Zinc is an essential trace element playing fundamental roles in cellular metabolism. It acts mostly by binding a wide range of proteins, thus affecting a broad spectrum of biological processes, which include cell division, growth and differentiation. Zinc is critical to a large number of structural proteins, enzymatic processes, and transcription factors. Zinc deficiency can result in a spectrum of clinical manifestations, such as poor of appetite, loss of body hair, altered taste and smell, testicular atrophy, cerebral and immune dysfunction, and diminished drug elimination capacity. These are common symptoms in patients with chronic liver diseases, especially liver cirrhosis. The liver is the main organ responsible for the zinc metabolism which can be affected by liver diseases. On the other hand, zinc deficiency may alter hepatocyte functions and also immune responses in inflammatory liver diseases. Liver cirrhosis represents the most advanced stage of chronic liver diseases and is the common outcome of chronic liver injury. It is associated with energy malnutrition, with numerous metabolic disorders, such as hypoalbuminemia, with imbalance between branched-chain amino acids and aromatic amino acids, and with reduced zinc serum concentrations. All these processes can influence the clinical outcome of patients, such ascites, hepatic encephalopathy and hepatocellular carcinoma. In the present review, we summarize the emerging evidence on the pitoval role of zinc in the pathogenesis of liver cirrhosis.
Russ, Kirk B.; Stevens, Todd M; Singal, Ashwani K.
Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK. PMID:26623266
Bunchorntavakul, Chalermrat; Chamroonkul, Naichaya; Chavalitdhamrong, Disaya
Bacterial infection is common and accounts for major morbidity and mortality in cirrhosis. Patients with cirrhosis are immunocompromised and increased susceptibility to develop spontaneous bacterial infections, hospital-acquired infections, and a variety of infections from uncommon pathogens. Once infection develops, the excessive response of pro-inflammatory cytokines on a pre-existing hemodynamic dysfunction in cirrhosis further predispose the development of serious complications such as shock, acute-on-chronic liver failure, renal failure, and death. Spontaneous bacterial peritonitis and bacteremia are common in patients with advanced cirrhosis, and are important prognostic landmarks in the natural history of cirrhosis. Notably, the incidence of infections from resistant bacteria has increased significantly in healthcare-associated settings. Serum biomarkers such as procalcitonin may help to improve the diagnosis of bacterial infection. Preventive measures (e.g., avoidance, antibiotic prophylaxis, and vaccination), early recognition, and proper management are required in order to minimize morbidity and mortality of infections in cirrhosis. PMID:26962397
Merrill, Jennifer E.; Wardell, Jeffrey D.; Read, Jennifer P.
Objective: Although college students experience a diverse range of alcohol consequences, most studies focus on global, rather than distinct, consequence types. One predictor of unique consequences—drinking motives—has been studied only cross-sectionally. We aimed to examine the prediction of unique alcohol consequence domains (social/interpersonal, academic/occupational, risky behavior, impaired control, poor self-care, diminished self-perception, blackout drinking, and physiological dependence) by coping and enhancement motives over the course of one year. We hypothesized that coping motives would directly predict and that enhancement motives would indirectly (through alcohol use) predict unique consequences. Method: Web surveys were administered to a sample of college students (n = 552, 62% female) at the beginning of the fall semester for 2 consecutive academic years. Structural equation modeling was used to test direct and indirect paths from motives to consequences. Results: The data supported hypothesized direct, prospective paths from coping motives to several alcohol consequences (impaired control, diminished self-perception, poor self-care, risky behaviors, academic/occupational, and physiological dependence). These associations were not mediated by alcohol consumption. Enhancement motives were indirectly associated with all eight consequence domains by way of increased alcohol use at follow-up. Models were invariant across gender, year in school, and symptoms of posttraumatic stress. Conclusions: Findings suggest that whether motives act as a final common pathway to problem drinking may depend on which motives and which drinking outcomes are examined. As coping motives demonstrate a direct link to unique alcohol problem types over time, individuals endorsing these motives may need to be prioritized for intervention. PMID:24411801
Many individuals wait until alcohol use becomes severe before treatment is sought. However, social networks, or the number of social groups an individual belongs to, may play a moderating role in this relationship. Logistic regression examined the interaction of alcohol consumption and social networks as a predictor of treatment utilization while adjusting for sociodemographic and clinical variables among 1,433 lifetime alcohol-dependent respondents from wave 2 of the National Epidemiologic Survey on Alcohol Related Conditions (NESARC). Results showed that social networks moderate the relationship between alcohol consumption and treatment utilization such that for individuals with few network ties, the relationship between alcohol consumption and treatment utilization was diminished, compared to the relationship between alcohol consumption and treatment utilization for individuals with many network ties. Findings offer insight into how social networks, at times, can influence individuals to pursue treatment, while at other times, influence individuals to stay out of treatment, or seek treatment substitutes.
Forster, Myriam; Unger, Jennifer B.; Sussman, Steve
Objective To conduct a systematic review of the literature examining risk and protective factors of alcohol related negative consequences (ARNCs) among adolescents. Methods We conducted a systematic search of original empirical articles published between January 1, 1990 and June 1, 2015. The qualitative synthesis was performed using the Theory of Triadic Influence as a framework. Results Fifty-two studies were reviewed. Intrapersonal (e.g., personality traits, drinking motives and expectancies, depression), interpersonal (e.g., parental and peer alcohol use, violence exposure) and attitudinal factors (e.g., media exposure to alcohol, religiosity) influence ARNCs. Emerging evidence of new trends contributing to ARNCs include ready mixed alcohol drinks and childhood trauma and abuse. Conclusions Risk factors from all domains of influence were observed. More research is needed on protective factors and how alcohol use interacts with preventive factors in predicting ARNCs. The conceptualization of negative consequences varies significantly between studies and may impact the external validity of previous research. PMID:26871952
Workers at the Swedish Telephone Company participated in the present study to explore the alcohol-related expectancies for a general sample of Swedish citizens and relate these expectancies to various background factors and whether the expected effects of alcohol also were desired effects. A slightly modified version of the Alcohol Expectancy Questionnaire (AEQ) was used and data were analyzed in terms of six general factors. Results indicated that men expected more sexual enhancement than women and that high consumers expected more strong effects for all six factors than the low consumers. Men further rated both sexual enhancement, physical and social pleasure, and social assertiveness as more desirable effects than did women, and the high consumers rated all six effects as more desirable than the low consumers. Results are discussed in terms of expectancies as causes of drinking.
Io, Aro; Yoshimoto, Hisashi
Japan passed the national law "Basic Act on Measures against Alcohol-related Health Harm" on December 2013. This law is expected to prevent inappropriate drinking that leads to alcohol-related problems such as physical and mental disorder, drunk driving, suicide, domestic violence, child abuse, and poor work performance. The physician's responsibilities under this law are described as follows: i) to provide high quality and appropriate medical care concerning alcohol-related health harm; ii) to reduce or eliminate the consumption of alcohol, thus preventing the progression of alcohol-related health harm; and iii) to coordinate these efforts amongst medical institutions. Based on this law, we believe that Japanese physicians will have essential roles in achieving the goals of this law and that we can fulfill our responsibilities by observing the following aspects: a) changing our message to the patients from "drink sensibly and moderately" to "low-risk drinking; but any drinking has a risk of harm and low-risk drinking is not risk-free"; b) encouraging the spread and use of Screening, Brief Intervention, and Referral to Treatment (SBIRT); and c) establishing community healthcare systems for alcohol-related problems, including dementia in the elderly and during alcohol emergencies.
Bozkurt, Muge; Evren, Cuneyt; Umut, Gokhan; Evren, Bilge
Purpose Attention-deficit/hyperactivity disorder (ADHD) has been shown to be related to a higher risk of developing psychiatric problems such as depressive disorders, substance use disorder, and impulsivity. Adults who have comorbid ADHD and alcohol use disorder (AUD) are at greater risk of negative outcomes. Thus, it is important to evaluate the relationship of ADHD symptoms and the severity of alcohol-related problems among patients with AUD. The aim of the present study was to evaluate the effect of ADHD symptoms on severity of alcohol-related problems, while controlling the effects of depression and impulsivity in a sample of inpatients with AUD. Patients and methods Participants (n=190) were evaluated with the Beck Depression Inventory, the Short Form Barratt Impulsiveness Scale, the Michigan Alcohol Screening Test, and the Adult ADHD Self-Report Scale. Results Severity of the scale scores was positively correlated with each other. Although severity of depression and impulsivity (particularly non-planning impulsivity) predicted the severity of alcohol-related problems in a linear regression model, when severity of ADHD symptoms was included in the analysis, the inattentive subscale score, in particular, predicted the severity of alcohol-related problems together with non-planning impulsivity, whereas depression was no longer a predictor. Conclusion These findings suggest that, together with non-planning impulsivity, symptoms of ADHD (particularly inattentive factor) are an important factor that predict alcohol-related problems, while controlling the severity of depressive symptoms among inpatients with AUD. PMID:27462159
Sacco, Paul; Unick, George Jay; Kuerbis, Alexis; Koru, A. Güneş; Moore, Alison A.
Objective This aim of this study was to characterize trends in alcohol-related hospital admissions among middle-aged and older adults from 1993 to 2010 in relation to age, gender, race, and cohort membership. Method This study utilized repeated cross-sectional data from the Nationwide Inpatient Sample. Using alcohol-related classified admissions, yearly rates and longitudinal trends of alcohol-related inpatient hospitalizations based on age, period, birth cohort, gender, and race were estimated. Results Among those aged 45 and older, admissions rose from an estimated 610,634 to more than 1,134,876, and rates of any alcohol-related diagnosis also increased from 1993 to 2010. Rates for men were consistently higher than women, and rates for Blacks were higher than Whites. Age was associated with decreasing rates, but post–World War II cohorts displayed higher rates over time. Discussion Rates of alcohol-related admissions are increasing among adults above age 45, which may be a function of cohort effects. Training the health care workforce is crucial to respond to this trend. PMID:25903980
Brown, Stephen L; Lipka, Sigrid; Coyne, Sarah M; Qualter, Pamela; Barlow, Alexandra; Taylor, Paul
Social scripts are commonly shared representations of behavior in social contexts, which are seen to be partly transmitted through social and cultural media. Research suggests that people hold scripts associated with alcohol-related aggression, but, unlike general aggression scripts, there is little evidence of social transmission. To demonstrate social transmission of alcohol-related aggression scripts, learning mechanisms based on personal experience should be minimized. We used a lexical decision task to examine implicit links between alcohol and aggression in alcohol-naïve adolescents who have limited personal or vicarious experience of alcohol-related aggression. One hundred and four 11-14 year old adolescents made lexical decisions on aggressive or nonaggressive words preceded by 40-ms alcohol or nonalcohol word primes. Repeated measures analyses of group data showed that alcohol word primes did not lead to faster responses to aggressive words than to nonaggressive words, nor were responses to aggressive words faster when they were preceded by alcohol word primes than by nonalcohol word primes. However, at an individual level, faster recognition times to the alcohol prime/aggression target word combination predicted aggression on a competitive laboratory task in 14 year olds only. This occurred only when the competitive aggression task was preceded by a visual presentation of alcoholic, but not nonalcoholic beverage, images. We concluded that alcohol-related aggression scripts are not strongly developed in this age group, but individual differences in script strength are linked to alcohol-related laboratory aggression.
Barnett, Nancy P.; Clerkin, Elise M.; Wood, Mark; Monti, Peter M.; O’Leary Tevyaw, Tracy; Corriveau, Donald; Fingeret, Allan; Kahler, Christopher W.
Objective: The purpose of this study was to establish the frequency of positive and negative alcohol-related consequences during the first year of college and to evaluate gender, race/ethnicity, time of year, alcohol use, and intoxication as predictors of consequences using frequent assessments. Method: Participants (N = 1,053; 57.5% female) completed biweekly assessments of alcohol use and positive and negative alcohol-related consequences throughout the year. Results: The majority of drinkers reported both positive and negative consequences. Having a good time and feeling less stressed were the most commonly reported positive consequences. Blackouts and getting physically sick were the most commonly endorsed negative consequences. At the weekly level, number of drinking days, drinks per drinking day, and estimated blood alcohol concentration (eBAC, reflecting intoxication) were significantly related to all consequences after controlling for demographics and time of year. Negative consequences had stronger associations with number of drinks and eBAC than positive consequences did. With each additional drink consumed on a drinking day, the incidence of negative consequences more than doubled (incidence rate ratio [IRR] = 2.34, 95% CI [2.19, 2.50]), whereas the incidence of positive consequences increased by about half (IRR = 1.51, 95% CI [1.47, 1.56]). The consequence with the largest gender difference was regretted sex, with women reporting it more often. Few racial/ethnic differences were found in report of negative consequences. Greater positive and negative consequences were endorsed at the beginning of both academic semesters. Conclusions: As number of drinks and eBAC increase, the relative odds of a negative consequence are higher than that of a positive consequence. Alcohol interventions could promote greater awareness of the likelihood of specific consequences and could highlight that positive consequences are associated with lower levels of drinking. PMID
Gates, Jonathan R.; Corbin, William R.; Fromme, Kim
Alcohol use generally peaks during the early twenties and declines with age. These declines, referred to as “maturing out,” are presumed to result from the acquisition of adult roles (e.g. marriage, employment) incompatible with alcohol use. Recent empirical evidence suggests that variables other than role transitions (e.g. personality) may also be important in understanding this process. Changes in identity that occur during emerging adulthood may also be linked to the process of maturing out of heavy drinking, though no studies have yet addressed this possibility. Utilizing data from a large sample of graduating college students (N = 907) during senior year (wave 1) and the two following years (waves 2-3), the current study examined relations between aspects of emerging adult identity and drinking outcomes (alcohol use and problems). Using time varying covariate growth models, results indicated that several facets of emerging adult identity conferred risk for the failure to mature out of heavy drinking and alcohol-related problems. Experimentation/possibilities emerged as a significant risk factor for both heavy drinking and alcohol problems, but these effects diminished considerably when accounting for personality risk. In contrast, although small in magnitude, effects of self-focus on heavy drinking and negativity/instability on alcohol-related problems were relatively independent of effects of other established predictors. The effect for negativity/instability was evident only at the final wave. The findings have important implications for theories of “maturing out” and may ultimately inform tailoring or refinement of prevention/intervention approaches for emerging adults. PMID:27077443
Gates, Jonathan R; Corbin, William R; Fromme, Kim
Alcohol use generally peaks during the early 20s and declines with age. These declines, referred to as "maturing out," are presumed to result from the acquisition of adult roles (e.g., marriage, employment) incompatible with alcohol use. Recent empirical evidence suggests that variables other than role transitions (e.g., personality) may also be important in understanding this process. Changes in identity that occur during emerging adulthood may also be linked to the process of maturing out of heavy drinking, though no studies have yet addressed this possibility. Utilizing data from a large sample of graduating college students (N = 907) during senior year (Wave 1) and the 2 following years (Waves 2-3), the current study examined relations between aspects of emerging adult identity and drinking outcomes (alcohol use and problems). Using time-varying covariate growth models, results indicated that several facets of emerging adult identity conferred risk for the failure to mature out of heavy drinking and alcohol-related problems. Experimentation/possibilities emerged as a significant risk factor for both heavy drinking and alcohol problems, but these effects diminished considerably when accounting for personality risk. In contrast, although small in magnitude, effects of self-focus on heavy drinking and negativity/instability on alcohol-related problems were relatively independent of effects of other established predictors. The effect for negativity/instability was evident only at the final wave. The findings have important implications for theories of maturing out and may ultimately inform tailoring or refinement of prevention/intervention approaches for emerging adults. (PsycINFO Database Record
Menvielle, Gwenn; Kunst, Anton E.; Stirbu, Irina; Borrell, Carme; Bopp, Matthias; Regidor, Enrique; Heine Strand, Bjørn; Deboosere, Patrick; Lundberg, Olle; Leclerc, Annette; Costa, Giuseppe; Chastang, Jean-Francois; Esnaola, Santiago; Martikainen, Pekka; Mackenbach, Johan P.
We aim to study socioeconomic inequalities in alcohol related cancers mortality (upper aero-digestive tract (UADT) (oral cavity, pharynx, larynx, oesophagus) and liver) in men and to investigate whether the contribution of these cancers to socioeconomic inequalities in cancer mortality differs within Western Europe. We used longitudinal mortality datasets including causes of death. Data were collected during the 1990s among men aged 30–74 years in 13 European populations (Madrid, the Basque region, Barcelona, Turin, Switzerland (German and Latin part), France, Belgium (Walloon and Flemish part, Brussels), Norway, Sweden, Finland). Socioeconomic status was measured using the educational level declared at the census at the beginning of the follow-up period. We conducted Poisson regression analyses and used both relative (Relative index of inequality (RII)) and absolute (mortality rates difference) measures of inequality. For UADT cancers, the RII’s were above 3.5 in France, Switzerland (both parts) and Turin whereas for liver cancer they were the highest (around 2.5) in Madrid, France and Turin. The contribution of alcohol related cancer to socioeconomic inequalities in cancer mortality was 29–36% in France and the Spanish populations, 17–23% in Switzerland and Turin, and 5–15% in Belgium and the Nordic countries. We did not observe any correlation between mortality rates differences for lung and UADT cancers, confirming that the pattern found for UADT cancers is not only due to smoking. This study suggests that alcohol use substantially influences socioeconomic inequalities in male cancer mortality in France, Spain and Switzerland but not in the Nordic countries and nor in Belgium. PMID:17415714
Gershwin, M E; Ansari, A A; Mackay, I R; Nakanuma, Y; Nishio, A; Rowley, M J; Coppel, R L
Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and ultimately fibrosis. The serologic hallmark of PBC is the presence of antibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex. The mechanisms by which (and if) such antibodies produce liver tissue injury are unknown. However, the presence of these antibodies has allowed detailed immunological definition of the antigenic epitopes, the nature of reactive autoantibodies and the characterization of T-cell responses. Several mechanisms may now be proposed regarding the immune-mediated bile duct damage in PBC, including the possible role of T-cell-mediated cytotoxicity and intracellular interaction between the IgA class of antimitochondrial antibodies and mitochondrial autoantigens. There are major questions which remain unanswered, including, of course, etiology, but also the reasons for female predominance, the absence of PBC in children, the relative ineffectiveness of immunosuppressive drugs, and the specific role of mitochondrial antigens. The data so far provide suggestive evidence that PBC is a mucosal disease; this thesis provides a basis for discussion of etiology via the enterohepatic circulation of toxins and/or infection.
Elkrief, Laure; Rautou, Pierre-Emmanuel; Sarin, Shiv; Valla, Dominique; Paradis, Valérie; Moreau, Richard
Disorders of glucose metabolism, namely glucose intolerance and diabetes, are frequent in patients with chronic liver diseases. In patients with cirrhosis, diabetes can be either a classical type 2 diabetes mellitus or the so-called hepatogenous diabetes, i.e. a consequence of liver insufficiency and portal hypertension. This review article provides an overview of the possible pathophysiological mechanisms explaining diabetes in patients with cirrhosis. Cirrhosis is associated with portosystemic shunts as well as reduced hepatic mass, which can both impair insulin clearance by the liver, contributing to peripheral insulin resistance through insulin receptors down-regulation. Moreover, cirrhosis is associated with increased levels of advanced-glycation-end products and hypoxia-inducible-factors, which may play a role in the development of diabetes. This review also focuses on the clinical implications of diabetes in patients with cirrhosis. First, diabetes is an independent factor for poor prognosis in patients with cirrhosis. Specifically, diabetes is associated with the occurrence of major complications of cirrhosis, including ascites and renal dysfunction, hepatic encephalopathy and bacterial infections. Diabetes is also associated with an increased risk of hepatocellular carcinoma in patients with chronic liver diseases. Last, the management of patients with concurrent diabetes and liver disease is also addressed. Recent findings suggest a beneficial impact of metformin in patients with chronic liver diseases. Insulin is often required in patients with advanced cirrhosis. However, the favourable impact of controlling diabetes in patients with cirrhosis has not been demonstrated yet.
Dirchwolf, Melisa; Ruf, Andrés Eduardo
The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure (ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts (evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted.
Dirchwolf, Melisa; Ruf, Andrés Eduardo
The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure (ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts (evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted. PMID:26261687
Sharma, Suraj; Khalili, Korosh; Nguyen, Geoffrey Christopher
Liver cirrhosis is a common and growing public health problem globally. The diagnosis of cirrhosis portends an increased risk of morbidity and mortality. Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis. However, despite its universal use, liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks. In order to overcome the limitations of liver biopsy, a number of non-invasive techniques have been investigated for the assessment of cirrhosis. This review will focus on currently available non-invasive markers of cirrhosis. The evidence behind the use of these markers will be highlighted, along with an assessment of diagnostic accuracy and performance characteristics of each test. Non-invasive markers of cirrhosis can be radiologic or serum-based. Radiologic techniques based on ultrasound, magnetic resonance imaging and elastography have been used to assess liver fibrosis. Serum-based biomarkers of cirrhosis have also been developed. These are broadly classified into indirect and direct markers. Indirect biomarkers reflect liver function, which may decline with the onset of cirrhosis. Direct biomarkers, reflect extracellular matrix turnover, and include molecules involved in hepatic fibrogenesis. On the whole, radiologic and serum markers of fibrosis correlate well with biopsy scores, especially when excluding cirrhosis or excluding fibrosis. This feature is certainly clinically useful, and avoids liver biopsy in many cases.
Rinaldi, Luca; Nascimbeni, Fabio; Giordano, Mauro; Masetti, Chiara; Guerrera, Barbara; Amelia, Annalisa; Fascione, Maria Chiara; Ballestri, Stefano; Romagnoli, Dante; Zampino, Rosa; Nevola, Riccardo; Baldelli, Enrica; Iuliano, Natalina; Rosato, Valerio; Lonardo, Amedeo; Adinolfi, Luigi Elio
AIM To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related cirrhosis. METHODS A prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an age- and Child-Pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography. All cases of cirrhosis without a definite etiology were enrolled in the CC group. The parameters assessed were: (1) severity of liver disease at the time of first diagnosis; (2) liver decompensation during follow-up; (3) hepatocellular carcinoma (HCC); (4) orthotopic liver transplantation; and (5) death. The independent associated factors were evaluated by multiple logistic regression analysis, and survival and its determinants by the Kaplan-Meier model, log-rank test and Cox regression. RESULTS At the first observation, median age was 66 and 65 years and male gender was 36% and 58% for CC and HCV cirrhosis, respectively. CC showed Child-Pugh class A/B/C of 47%/31%/22%, respectively. Compared to HCV cirrhosis, CC exhibited a significantly higher prevalence of metabolic syndrome (12% vs 54%, respectively), overweight/obesity, high BMI, impaired glucose tolerance, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones. Over a median period of 42 mo of follow-up, liver decompensation, HCC development and death for CC and HCV-related cirrhosis were 60.8%, and 54.4%, 16.7% and 17.2%, 39.2% and 30%, respectively. The median survival was 60 mo for CC. Independent predictors of death were age and Child-Pugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-Pugh class A
Shen, Jiliang; Huang, Chiung-Kuei; Yu, Hong; Shen, Bo; Zhang, Yaping; Liang, Yuelong; Li, Zheyong; Feng, Xu; Zhao, Jie; Duan, Lian; Cai, Xiujun
Exosomes are small vesicles that were initially thought to be a mechanism for discarding unneeded membrane proteins from reticulocytes. Their mediation of intercellular communication appears to be associated with several biological functions. Current studies have shown that most mammalian cells undergo the process of exosome formation and utilize exosome-mediated cell communication. Exosomes contain various microRNAs, mRNAs and proteins. They have been reported to mediate multiple functions, such as antigen presentation, immune escape and tumour progression. This concise review highlights the findings regarding the roles of exosomes in liver diseases, particularly hepatitis B, hepatitis C, liver cirrhosis and hepatocellular carcinoma. However, further elucidation of the contributions of exosomes to intercellular information transmission is needed. The potential medical applications of exosomes in liver diseases seem practical and will depend on the ingenuity of future investigators and their insights into exosome-mediated biological processes.
Zhang Jinsong Wang Huali; Yu Hanqing
Selenium reduction in cirrhosis is frequently reported. The known beneficial effect of selenium supplementation on cirrhosis is probably obtained from nutritionally selenium-deficient subjects. Whether selenium supplementation truly improves cirrhosis in general needs additional experimental investigation. Thioacetamide was used to induce cirrhosis in selenium-adequate and -deficient mice. Selenoenzyme activity and selenium content were measured and the influence of selenium supplementation was evaluated. In Se-adequate mice, thioacetamide-mediated rapid onset of hepatic oxidative stress resulted in an increase in thioredoxin reductase activity and a decrease in both glutathione peroxidase activity and selenium content. The inverse activity of selenoenzymes (i.e. TrxR activity goes up and GPx activity goes down) was persistent and mute to selenium supplementation during the progress of cirrhosis; accordingly, cirrhosis was not improved by selenium supplementation in any period. On the other hand, selenium supplementation to selenium-deficient mice always more efficiently increased hepatic glutathione peroxidase activity and selenium content compared with those treated with thioacetamide, indicating that thioacetamide impairs the liver bioavailability of selenium. Although thioacetamide profoundly affects hepatic selenium status in selenium-adequate mice, selenium supplementation does not modify the changes. Selenium supplementation to cirrhotic subjects with a background of nutritional selenium deficiency can improve selenium status but cannot restore hepatic glutathione peroxidase and selenium to normal levels.
Cherpitel, Cheryl J.; Ye, Yu; Kerr, William
Objective: National population data on racial/ethnic disparities and risk of alcohol-related injury are scarce. Alcohol-related injury and drinking patterns are examined in a sample of respondents from four (1995, 2000, 2005, 2010) U.S. National Alcohol Surveys using risk function analysis. Method: Self-reported consumption of 15,476 current drinkers was assessed as the average number of drinks consumed monthly and, separately, the frequency of consuming five or more drinks in a day (5+ days) in the last year. Alcohol-related injury was defined as drinking within 6 hours before the event. Risk curves were defined, separately for Whites, Blacks, and Hispanics, using fractional polynomial regression. Results: Risk was greatest for Hispanics to 110 drinks per month (3–4 drinks per day) and above 240 drinks per month, whereas risk was greatest for Whites between these levels. Blacks were at lower risk at all monthly volume levels when demographic and socioeconomic status characteristics were controlled for. Whites had the highest risk of an alcohol-related injury based on 5+ drinking days at all levels up to nearly daily 5+ drinking, whereas Blacks had the lowest risk at all levels of 5+ drinking. Conclusions: A disparity in alcohol-related injury was found for Hispanics compared with Whites at the same average monthly volume of consumption at lower and higher volume levels, but not at the same number of 5+ drinking days, and a lower risk of alcohol-related injury was found for Blacks for both consumption measures when demographic and socioeconomic status characteristics were taken into account. Although exposure to hazards other than alcohol, which could account for some of the racial/ethnic disparity observed, was not taken into account, these mixed findings suggest this is an important area deserving future research attention. PMID:26751355
Background This study examines whether alcohol-related hospitalization predicts survey non-response, and evaluates whether this missing data result in biased estimates of the prevalence of hazardous alcohol use and abstinence. Methods Registry data on alcohol-related hospitalizations during the preceding ten years were linked to two representative surveys. Population data corresponding to the surveys were derived from the Stockholm County registry. The alcohol-related hospitalization rates for survey responders were compared with the population data, and corresponding rates for non-responders were based on the differences between the two estimates. The proportions with hazardous alcohol use and abstinence were calculated separately for previously hospitalized and non-hospitalized responders, and non-responders were assumed to be similar to responders in this respect. Results Persons with previous alcohol-related admissions were more likely currently to abstain from alcohol (RR=1.58, p<.001) or to have hazardous alcohol use (RR=2.06, p<.001). Alternatively, they were more than twice as likely to have become non-responders. Adjusting for this skewed non-response, i.e., the underrepresentation of hazardous users and abstainers among the hospitalized, made little difference to the estimated rates of hazardous use and abstinence in total. During the ten-year period 1.7% of the population were hospitalized. Conclusions Few people receive alcohol-related hospital care and it remains unclear whether this group’s underrepresentation in surveys is generalizable to other groups, such as hazardous users. While people with severe alcohol problems – i.e. a history of alcohol-related hospitalizations – are less likely to respond to population surveys, this particular bias is not likely to alter prevalence estimates of hazardous use. PMID:23497679
Hoffman, Eric W; Austin, Erica Weintraub; Pinkleton, Bruce E; Austin, Bruce W
College students' use of digital communication technology has led to a rapid expansion of digital alcohol marketing efforts. Two surveys (total usable n = 637) were conducted to explore college students' experiences with alcohol-related social media, their decision making related to alcohol use, and their problematic drinking behaviors. Study results indicated that students' use of alcohol-related social media predicted their problem drinking behaviors. In addition, students' wishful identification, perceived desirability, perceived similarity, and normative beliefs predicted their expectancies for drinking alcohol. Finally, students' expectancies for drinking alcohol predicted their problematic drinking behaviors.
Chang, Li-Yuan; Li, Yonghai; Kaplan, David E.
Peripheral CD27+ memory B-cells become quantitatively reduced and dysfunctional in patients with cirrhosis through poorly characterized mechanisms. We hypothesized that the disappearance of CD27+ memory B-cells results from enhanced sensitivity to apoptosis caused by exposure to gut microbial translocation products. Using isolated naïve and memory B-cells from patients with cirrhosis and age-matched controls, ex vivo and activation-induced sensitivity to Fas-mediated apoptosis was assessed under relevant experimental conditions. We observed differential expression of CD95(Fas) in CD27+ B-cells from cirrhotic patients that was inversely correlated with peripheral CD27+ B-cell frequency. While memory B-cells from cirrhotic patients were resistant to Fas-mediated apoptosis ex vivo, Toll-like receptor 4(TLR4)-ligation restored Fas-sensitivity. Sensitivity to Fas-mediated apoptosis could be transferred to healthy donor memory B-cells by co-culturing these cells with plasma from cirrhotic patients, a sensitivity partially mediated by Fas and TLR4 signaling, and partially rescued via B-cell receptor crosslinking. We conclude that peripheral CD27+ memory B-cells in cirrhosis exhibit increased sensitivity to Fas-induced apoptosis in an activation-dependent manner to which endotoxin contributes, associated with reduced frequency of circulating memory B-cells. Destruction of this critical cell subset may contribute to the cirrhotic immunodeficiency state and heightened risk of systemic infections in advanced liver disease. PMID:27857173
Sun, Ying; Zhang, Weici; Li, Baosen; Zou, Zhengsheng; Selmi, Carlo; Gershwin, M Eric
Organ-specific and systemic autoimmune diseases share numerous features and often coexist in the same patient. Autoimmune cholangitis/primary biliary cirrhosis and Sjogren syndrome represent paradigmatic examples of the common grounds of different autoimmunity phenotypes based on similarities in clinical manifestations and immunopathogenesis. In fact, primary biliary cirrhosis and Sjogren's syndrome have both been coined as an autoimmune epithelitis in which apoptosis may be in both cases the key element to explain the organ-specific immune-mediated injury against the biliary and exocrine gland epithelia, respectively. Further, growing evidence supports in both diseases the view that B cells, T cytotoxic cells, and T helper cells are involved in chronic inflammation, likely via the altered expression of pro-inflammatory cytokines. The presence of estrogen receptors on the biliary and exocrine gland epithelia has been advocated as a key to the female predominance encountered in primary biliary cirrhosis and Sjogren's syndrome. Sadly, despite available data, therapeutic approaches remain largely unsatisfactory and recent studies with mechanistic approaches (as in the case of B cell depletion with rituximab) have been of partial benefit only. Future studies should focus on new molecular tools (single-cell transcriptomics, microRNA, epigenetics) to provide unique insights into common mechanisms.
Hung, Tzu-Min; Yuan, Ray-Hwang; Huang, Wei-Pang; Chen, Yu-Hsuan; Lin, Yu-Chun; Lin, Chih-Wen; Lai, Hong-Shiee; Lee, Po-Huang
Autophagy is a regulatory pathway in liver fibrosis. We investigated the roles of autophagy in human cirrhotic livers. Cirrhotic and noncirrhotic liver tissues were obtained from patients with hepatocellular carcinoma, and liver tissues from live donors served as control. Patients with cirrhotic livers had significantly increased levels of various essential autophagy-related genes compared with noncirrhotic livers. In addition, colocalization of autophagy marker microtubule-associated protein 1 light chain 3B (LC3B) with lysosome-associated membrane protein-1, increased levels of lysosome-associated membrane protein-2, and increased maturation of lysosomal cathepsin D were observed in cirrhotic livers. By using dual-immunofluorescence staining, we demonstrated that increased LC3B was located mainly in the cytokeratin 19-labeled ductular reaction (DR) in human cirrhotic livers and in an experimental cirrhosis induced by 2-acetylaminofluorene (AAF) with carbon tetrachloride (CCl4), indicating a conserved response to chronic liver damage. Furthermore, an AAF/CCl4-mediated increase in DR and fibrosis were attenuated after chloroquine treatment, suggesting that the autophagy-lysosome pathway was essential for AAF/CCl4-induced DR-fibrosis. In conclusion, we demonstrated that increased autophagy marker positively correlated with DR during the development of cirrhosis. Therefore, targeting autophagy may hold therapeutic value for liver cirrhosis.
Wang, Lifeng; Wang, Fu-Sheng; Chang, Christopher; Gershwin, M Eric
In primary biliary cirrhosis (PBC), the breach of tolerance that leads to active disease involves a disruption in several layers of control, including central tolerance, peripheral anergy, a "liver tolerance effect," and the action of T regulatory cells and their related cytokines. Each of these control mechanisms plays a role in preventing an immune response against self, but all of them act in concert to generate effective protection against autoimmunity without compromising the ability of the host immune system to mount an effective response to pathogens. At the same time, genetic susceptibility, environmental factors, including infection agents and xenobiotics, play important roles in breach of tolerance in the development of PBC.
Juakiem, Wassem; Torres, Dawn M; Harrison, Stephen A
Nutrition has not been a primary focus of many medical conditions despite its importance in the development and the severity of these diseases. This is certainly the case with nutrition and end-stage liver disease despite the well-established association of nutritional deficiencies and increased rates of complications and mortality in cirrhosis. This review provides an overview of nutrition in chronic liver disease with an emphasis on its pathogenesis as well as ways to assess nutritional status and intervene in an effort to improve nutrition.
Faiyaz, U.; Goyal, P.C.
The source of massive pleural effusion was not apparent in a 58-year-old man who had cirrhosis but no demonstrable ascites. Intraperitoneal injection of technetium Tc 99m sulfur colloid established the presence of peritoneopleural communication. This diagnostic technique can be helpful in evaluating patients with cirrhosis of the liver and pleural effusion with or without ascites.
Holmes, John; Green, Mark; Strong, Mark; Pearson, Tim; Meier, Petra
Background Availability of alcohol is a major policy issue for governments, and one of the availability factors is the density of alcohol outlets within geographic areas. Objective The aim of this study is to investigate the association between alcohol outlet density and hospital admissions for alcohol-related conditions in a national (English) small area level ecological study. Methods This project will employ ecological correlation and cross-sectional time series study designs to examine spatial and temporal relationships between alcohol outlet density and hospital admissions. Census units to be used in the analysis will include all Lower and Middle Super-Output Areas (LSOAs and MSOAs) in England (53 million total population; 32,482 LSOAs and 6781 MSOAs). LSOAs (approximately 1500 people per LSOA) will support investigation at a fine spatial resolution. Spatio-temporal associations will be investigated using MSOAs (approximately 7500 people per MSOA). The project will use comprehensive coverage data on alcohol outlets in England (from 2003, 2007, 2010, and 2013) from a commercial source, which has estimated that the database includes 98% of all alcohol outlets in England. Alcohol outlets may be classified into two broad groups: on-trade outlets, comprising outlets from which alcohol can be purchased and consumed on the premises (eg, pubs); and off-trade outlets, in which alcohol can be purchased but not consumed on the premises (eg, off-licenses). In the 2010 dataset, there are 132,989 on-trade and 51,975 off-trade outlets. The longitudinal data series will allow us to examine associations between changes in outlet density and changes in hospital admission rates. The project will use anonymized data on alcohol-related hospital admissions in England from 2003 to 2013 and investigate associations with acute (eg, admissions for injuries) and chronic (eg, admissions for alcoholic liver disease) harms. The investigation will include the examination of conditions that
Kumar, Naveen; Choudhary, Narendra Singh
The problem of obesity is increasing worldwide in epidemic proportions; the situation is similarly becoming more common in patients with cirrhosis which negatively affect the prognosis of disease and also makes liver transplantation difficult especially in the living donor liver transplantation setting where low graft to recipient weight ratio negatively affects survival. Treatment of obesity is difficult in cirrhosis due to difficulty in implementation of lifestyle measures, limited data on safety of anti-obesity drugs and high risk of surgery. Currently approved anti-obesity drugs have limited data in patients with cirrhosis. Bariatric surgery remains an option in selected compensated cirrhotic patients. Endoscopic interventions for obesity are emerging and are quite promising in patients with cirrhosis as these are minimally invasive. In present review, we briefly discuss various modalities of weight reduction in obese patients and their applicability in patients with cirrhosis. PMID:26668693
Garcia-Tsao, Guadalupe; Wiest, Reiner
The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Cirrhotic patients are prone to develop bacterial infections, mainly the 'spontaneous' infection of ascites or spontaneous bacterial peritonitis. Other complications of cirrhosis, such as variceal haemorrhage and ascites, occur mostly or solely as a consequence of portal hypertension. Portal pressure increases initially as a consequence of an increased intrahepatic resistance but, once collaterals have formed, high portal pressure is maintained by an increased splanchnic blood inflow secondary to vasodilatation. Splanchnic vasodilatation is the initiating event in the hyperdynamic circulatory state that aggravates the complications of cirrhosis. The gut flora plays a role in both the development of infections and in the hyperdynamic circulatory state of cirrhosis and, although less prominently, it also plays a role in the pathogenesis of hepatic encephalopathy. This chapter presents evidence regarding gut flora and its modification in the pathogenesis and management of these complications of cirrhosis.
Bhat, Mamatha; Arendt, Bianca M; Bhat, Venkat; Renner, Eberhard L; Humar, Atul; Allard, Johane P
The intestinal microbiome (IM) is altered in patients with cirrhosis, and emerging literature suggests that this impacts on the development of complications. The PubMed database was searched from January 2000 to May 2015 for studies and review articles on the composition, pathophysiologic effects and therapeutic modulation of the IM in cirrhosis. The following combination of relevant text words and MeSH terms were used, namely intestinal microbiome, microbiota, or dysbiosis, and cirrhosis, encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, variceal bleeding, hepatopulmonary syndrome, portopulmonary hypertension and hepatocellular carcinoma. The search results were evaluated for pertinence to the subject of IM and cirrhosis, as well as for quality of study design. The IM in cirrhosis is characterized by a decreased proportion of Bacteroides and Lactobacilli, and an increased proportion of Enterobacteriaceae compared to healthy controls. Except for alcoholic cirrhosis, the composition of the IM in cirrhosis is not affected by the etiology of the liver disease. The percentage of Enterobacteriaceae increases with worsening liver disease severity and decompensation and is associated with bacteremia, spontaneous bacterial peritonitis and hepatic encephalopathy. Lactulose, rifaximin and Lactobacillus-containing probiotics have been shown to partially reverse the cirrhosis associated enteric dysbiosis, in conjunction with improvement in encephalopathy. The IM is altered in cirrhosis, and this may contribute to the development of complications associated with end-stage liver disease. Therapies such as lactulose, rifaximin and probiotics may, at least partially, reverse the cirrhosis-associated changes in the IM. This, in turn, may prevent or alleviate the severity of complications. PMID:27721918
Surgery in the patient with cirrhosis is problematic, as encephalopathy, ascites, sepsis and bleeding are common in the postoperative period. Accurate preoperative assessment and planning, and careful postoperative management have the potential to reduce the frequency and severity of such complications, and reduce the length of hospital stay, but there is little literature evidence to prove this. Operative mortality and other risks correlate with the severity of the liver disease, co-morbidities and the type of surgery. The Child-Turcott-Pugh (CTP) score or model for end-stage liver disease (MELD) score may be used to determine the severity of the liver disease, but must also take into account recent changes in the patient's condition. Surgery that does not involve opening the peritoneum may have slightly better outcomes, as the risk of ascitic leak, sepsis and difficult fluid management are reduced. Mortality rates range from 10% in CTP-A patients to 82% in CTP-C patients. The presence of portal hypertension is an important negative predictor, especially in abdominal surgery, as refractory ascites may occur. Careful monitoring in the postoperative period and early intervention of complications are essential. Hepatic resections in cirrhosis are associated with other considerations such as leaving sufficient liver tissue to prevent liver failure, and are beyond the scope of this review.
Kouroumalis, Elias; Notas, George
Primary biliary cirrhosis (PBC) is a chronic non-suppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient’s genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated. A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed. PMID:26261733
Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry
Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of “inflammatory stress” and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value. PMID:26019739
Nilius, R; Bernhardt, H; Zipprich, B; Knoke, M
23 patients with liver cirrhosis of diverse etiology and of different activity levels and grades of compensation of the portal circulation were examined with regard to the systemic endotoxinaemia. The endotoxin was determined using the Limulus-Amoebocyte-Lysat-test. Endotoxin was traceable in the venous blood of 7 out of 23 patients (= 30,4%). No relation was found between endotoxaemia and the activity or grade of severity of liver cirrhosis; nor were there any accumulation of endotoxinaemia in patients with collateral circulation or portal decompensation. Consequently, as a result of our findings, the prognostic value of the symptom endotoxinaemia remains debatable, then endotoxinaemia does not always mean endotoxicosis. Particularly high immunoglobulin concentration and low albumin values in serum of endotoxin-positive cirrhotics indicate a "spillovet" of antigen substances and also of endotoxines in the body circulation resulting from insufficiency of the liver-RHS. Parallel analysis of microbian small bowel flora in 10 patients indicate that coli-dysbiosis appears to play a role in the development of systemic endoxinaemia, although the latter was also traceable in borderline cases of eubiosis/dysbiosis. Our findings strengthen the view that it is not possible to simply translate the findings in animals on to human liver diseases. Quite a number of the mechanisms being discussed are still with uncleared details and they give only a blurred picture of the pathophysiology of endotoxinaemia.
Chen, L P; Zhao, H; Lyu, B; Cheng, J L
The complex interplay between immune factors and genetic susceptibility plays an essential role in autoimmune diseases. This is especially true for primary biliary cirrhosis (PBC). PBC is an autoimmune cholestatic liver disease characterized by the destruction of the small intrahepatic bile ducts and the presence of high-titer antimitochondrial antibodies (AMA). Among the currently known risk factors, genetic predisposition remains to be the dominant one. However, it is insufficient to explain the different geographic distributions of PBC and the incomplete concordance in identical twins. This suggests an association between specific environmental factors and the development of PBC. Nevertheless, a clear and rational association of environmental factors with primary biliary cirrhosis has not yet been fully elucidated. Our current understanding of the environmental triggers of PBC is limited to numerous suspected factors involved in its development, such as xenobiotics, electrophilic drugs, infection, and other physical, chemical, and even biological factors. Although the factors leading to the breakdown of immune tolerance in PBC are still largely unknown, related geoepidemiological studies may help us better understand the impact of the environment. In addition, a better understanding of the interplay between environmental factors and PBC is the critical step toward improving our management and control of PBC and autoimmunity in general.
Nardone, Raffaele; Höller, Yvonne; Storti, Monica; Lochner, Piergiorgio; Tezzon, Frediano; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen
A severe spinal cord involvement may rarely occur in patients with cirrhosis and other chronic liver diseases; this complication is usually associated with overt liver failure and surgical or spontaneous porto-systemic shunt. Hepatic myelopathy (HM) is characterized by progressive weakness and spasticity of the lower extremities, while sensory and sphincter disturbances have rarely been described and are usually less important. The diagnosis is assigned in the appropriate clinical setting on clinical grounds after the exclusion of other clinical entities leading to spastic paraparesis. Magnetic resonance imaging is often unremarkable; however, also intracerebral corticospinal tract abnormalities have been reported recently. The study of motor evoked potentials may disclose central conduction abnormalities even before HM is clinically manifest. HM responds poorly to blood ammonia-lowering and other conservative medical therapy. Liver transplantation represents a potentially definitive treatment for HM in patients with decompensated cirrhosis of Child-Pugh B and C grades. Other surgical treatment options in HM include surgical ligation, shunt reduction, or occlusion by interventional procedures.
Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry
Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of "inflammatory stress" and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value.
Gómez-Hurtado, Isabel; Such, José; Francés, Rubén
Qualitative and quantitative changes in gut microbiota play a very important role in cirrhosis. Humans harbour around 100 quintillion gut bacteria, thus representing around 10 times more microbial cells than eukaryotic ones. The gastrointestinal tract is the largest surface area in the body and it is subject to constant exposure to these living microorganisms. The existing symbiosis, proven by the lack of proinflammatory response against commensal bacteria, implies the presence of clearly defined communication lines that contribute to the maintenance of homeostasis of the host. Therefore, alterations of gut flora seem to play a role in the pathogenesis and progress of multiple liver and gastrointestinal diseases. This has made its selective modification into an area of high therapeutic interest. Bacterial translocation is defined as the migration of bacteria or bacterial products from the intestines to the mesenteric lymph nodes. It follows that alteration in gut microbiota have shown importance, at least to some extent, in the pathogenesis of several complications arising from terminal liver disease, such as hepatic encephalopathy, portal hypertension and spontaneous bacterial peritonitis. This review sums up, firstly, how liver disease can alter the common composition of gut microbiota, and secondly, how this alteration contributes to the development of complications in cirrhosis.
Gómez-Hurtado, Isabel; Such, José; Sanz, Yolanda; Francés, Rubén
Gut microbiota plays an important role in cirrhosis. The liver is constantly challenged with commensal bacteria and their products arriving through the portal vein in the so-called gut-liver axis. Bacterial translocation from the intestinal lumen through the intestinal wall and to mesenteric lymph nodes is facilitated by intestinal bacterial overgrowth, impairment in the permeability of the intestinal mucosal barrier, and deficiencies in local host immune defences. Deranged clearance of endogenous bacteria from portal and systemic circulation turns the gut into the major source of bacterial-related complications. Liver function may therefore be affected by alterations in the composition of the intestinal microbiota and a role for commensal flora has been evidenced in the pathogenesis of several complications arising in end-stage liver disease such as hepatic encephalopathy, splanchnic arterial vasodilatation and spontaneous bacterial peritonitis. The use of antibiotics is the main therapeutic pipeline in the management of these bacteria-related complications. However, other strategies aimed at preserving intestinal homeostasis through the use of pre-, pro- or symbiotic formulations are being studied in the last years. In this review, the role of intestinal microbiota in the development of the most frequent complications arising in cirrhosis and the different clinical and experimental studies conducted to prevent or improve these complications by modifying the gut microbiota composition are summarized.
Wintemute, Garen J; Wright, Mona A; Castillo-Carniglia, Alvaro; Shev, Aaron; Cerdá, Magdalena
Firearm violence frequently involves alcohol, but there are no studies of misuse of alcohol and risk for future violence among firearm owners. We examined the association between prior convictions for alcohol-related crimes, chiefly driving under the influence (DUI), and risk of subsequent arrest among 4066 individuals who purchased handguns in California in 1977. During follow-up through 1991, 32.8% of those with prior alcohol-related convictions and 5.7% of those with no prior criminal history were arrested for a violent or firearm-related crime; 15.9% and 2.7%, respectively, were arrested for murder, rape, robbery or aggravated assault. Prior alcohol-related convictions were associated with a fourfold to fivefold increase in risk of incident arrest for a violent or firearm-related crime, a relative increase greater than that seen for age, sex or prior violence. Prior convictions for alcohol-related crime may be an important predictor of risk for future criminal activity among purchasers of firearms.
Hermos, J.; Winter, M.; Heeren, T.; Hingson, R.
The authors determined whether lifetime prescription drug misuse (PDM) associated with increased risks for alcohol-related problems among 18- to 34-year-old, NESARC respondents. Among 8222 "ever-drinkers," 15.4% reported ever "misusing sedatives, tranquilizers, painkillers or stimulants ... as prescriptions or from indirect sources." Outcomes were…
LaAsmar v. Phelps Dodge Corp. Life, Accidental Death & Dismemberment & Dependent Life Ins. Plan, 605 F3d 789, 2010 WL 1794437(10th Cir. 2010). A death caused by an alcohol-related automobile collision qualifies as an "accident" that would require payment of accidental death and dismemberment plan benefits.
Peterson, Roselyn; Russo, Joan; Darnell, Doyanne; Wang, Jin; Ingraham, Leah; Zatzick, Douglas
Objective Approximately 30 million Americans present to acute care medical settings annually after incurring traumatic injuries. Posttraumatic stress disorder and depressive symptoms are endemic among injury survivors. Our paper is a replication and extension of a previous report documenting a pattern of multiple traumatic life events across patients admitted to Level I trauma centers for an alcohol-related injury. Method This study is a secondary analysis of a nationwide 20-site randomized trial of an alcohol brief intervention with 660 traumatically injured inpatients. Pre-injury trauma history was assessed using the National Comorbidity Survey trauma history screen at the 6 month time point. Results Most common traumatic events experienced by our population of alcohol positive trauma survivors were having had someone close unexpectedly die, followed by having seen someone badly beaten or injured. Of particular note, there is high reported prevalence of rape/sexual assault, and childhood abuse and neglect among physically injured trauma survivors. Additional trauma histories are increasingly common among alcohol-positive patients admitted for a traumatic injury. Conclusions Due to the high rate of experienced multiple traumatic events among acutely injured inpatients, the trauma history screen could be productively integrated into screening and brief intervention procedures developed for acute care settings. PMID:26745689
Vaeth, Patrice A C; Caetano, Raul; Mills, Britain A; Rodriguez, Lori A
This paper examines alcohol-related social problems among Mexican Americans living along the U.S.-Mexico border and in non-border areas. Interviews were conducted among Mexican Americans in the border regions of California, Arizona, New Mexico, and Texas (N=1307). Non-border respondents were interviewed primarily in Houston and Los Angeles (N=1288) as part of the Hispanic Americans Baseline Alcohol Survey (HABLAS). Both the border and HABLAS surveys employed multistage cluster sample designs (response rates were 67% and 76%, respectively). In the bivariate analysis, there were no significant differences between border and non-border areas in the proportion of those with one or more social problem. In non-border areas, the prevalence of alcohol problems did not differ significantly by age. However, along the border the prevalence of alcohol problems was significantly different across age groups, with 18 to 29year old men and women having the highest prevalence. The final models showed no residence effect on problem likelihood. Drinking was strongly associated with problems. Although young border residents had higher problem prevalence rates than older residents, the logistic regression models showed no effect of border residence on the likelihood of problems, indicating that problems are due to alcohol consumption, not the border environment. The border, however, did appear to influence more drinking among young people. Regardless of residence, alcohol treatment and preventive interventions tailored to Mexican Americans are essential and special attention should be focused on younger individuals near the border.
Attwood, Angela S; Munafò, Marcus R
The negative consequences of chronic alcohol abuse are well known, but heavy episodic consumption ("binge drinking") is also associated with significant personal and societal harms. Aggressive tendencies are increased after alcohol but the mechanisms underlying these changes are not fully understood. While effects on behavioural control are likely to be important, other effects may be involved given the widespread action of alcohol. Altered processing of social signals is associated with changes in social behaviours, including aggression, but until recently there has been little research investigating the effects of acute alcohol consumption on these outcomes. Recent work investigating the effects of acute alcohol on emotional face processing has suggested reduced sensitivity to submissive signals (sad faces) and increased perceptual bias towards provocative signals (angry faces) after alcohol consumption, which may play a role in alcohol-related aggression. Here we discuss a putative mechanism that may explain how alcohol consumption influences emotional processing and subsequent aggressive responding, via disruption of orbitofrontal cortex (OFC)-amygdala connectivity. While the importance of emotional processing on social behaviours is well established, research into acute alcohol consumption and emotional processing is still in its infancy. Further research is needed and we outline a research agenda to address gaps in the literature.
Parks, Kathleen A.; Levonyan-Radloff, Kristine; Dearing, Ronda L.; Hequembourg, Amy; Testa, Maria
Objective Using an iterative process, a series of three video scenarios were developed for use as a standardized measure for assessing women’s perception of risks for alcohol-related sexual assault (SA). The videos included ambiguous and clear behavioral and environmental risk cues. Method Focus group discussions with young, female heavy drinkers (N = 42) were used to develop three videos at different risk levels (low, moderate, and high) in Study 1. Realism, reliability, and validity of the videos were assessed using multiple methods in Studies 2 and 3. One hundred-four women were used to compare differences in risk perception across the video risk level in Study 2. In Study 3 (N = 60), we assessed women’s perceptions of the low and high risk videos under conditions of no alcohol and alcohol. Results The realism and reliability of the videos were good. Women who viewed the low risk video compared to women who viewed the moderate and high risk videos perceived less risk for SA. We found an interaction between alcohol and risk perception such that, women in the alcohol condition were less likely to perceive risk when watching the high risk video. Conclusions As the video risk level increased, women’s perception of risk increased. These findings provide convergent evidence for the validity of the video measure. Given the limited number of standardized scenarios for assessing risk perception for sexual assault, our findings suggest that these videos may provide a needed standardized measure. PMID:27747131
Elifson, Kirk W.
Purpose. This study examines the prevalence of alcohol-related problems, the factors underlying these problems, and whether or not there is evidence of syndemic effects in a community population of southern, urban African American women. Methods. Questionnaire-based interviews were conducted with 817 women, all African American, from 80 targeted census block groups in Atlanta, Georgia. Results. Most of the alcohol users (67.8%) experienced at least one problem as a result of their alcohol (ab)use, with most women experiencing two or more such problems. Eight factors were found to be associated with experiencing more alcohol problems: being aged 30 or older, having had no recent health insurance, lower levels of educational attainment, self-identifying as lesbian or bisexual, experiencing greater amounts of childhood maltreatment, greater impulsivity, perceiving one's local community or neighborhood to be unsafe, and having a larger number of criminally involved friends. Conclusions. Drinking-related problems were prevalent in this population. Numerous factors underlie the extent to which African American women experienced problems resulting from their alcohol use. There is strong evidence of syndemic-type effects influencing drinking problems in this population, and future efforts to reduce the negative impact of alcohol (ab)use ought to consider the adoption of programs using a syndemics' theory approach. PMID:27752388
Duarte-Rey, Carolina; Bogdanos, Dimitrios; Yang, Chen-Yen; Roberts, Krista; Leung, Patrick S.C.; Anaya, Juan-Manuel; Worman, Howard J.; Gershwin, M. Eric
Experimental models of autoimmune diseases have led to the conclusion that an immune response to nuclear antigens is a sentinel marker for loss of tolerance and potential tissue damage. Various proteins are targets of antinuclear antibodies in a variety of autoimmune diseases, ranging from systemic rheumatologic disorders to diseases affecting specific organs such as the liver. Autoantibodies against specific nuclear constituents have also been used as probes to understand the structure and the function of the targeted components and their relevance to disease pathogenesis. Approximately a quarter of patients with primary biliary cirrhosis (PBC) have antibodies targeting proteins of the nuclear pore complex (NPC), a multi-protein structure that mediates molecular transport across the nuclear envelope. Autoantibodies against the integral membrane glycoprotein gp210 and nucleoporin p62 appear to be highly specific for PBC, an autoimmune disease characterized by progressive destruction of intrahepatic biliary epithelial cells. This review discusses the diagnostic and clinical relevance of anti-NPC antibodies in PBC and the possibility that this autoimmune response may arise as a result of molecular mimicry. PMID:22487189
BARNETT, NANCY P.; GOLDSTEIN, ABBY L.; MURPHY, JAMES G.; COLBY, SUZANNE M.; MONTI, PETER M.
Objective Alcohol use and its associated behaviors are among the most common reasons for medical treatment and disciplinary infractions among college students. The purpose of this study was to describe the characteristics of students who had recent serious alcohol-related incidents and to identify predictors of motivation to change alcohol use and heavy drinking in particular, with specific attention to gender. Method Students (N = 227; 52% female) who had been mandated to attend a session of alcohol education following alcohol-related medical treatment and/or a disciplinary infraction were assessed on their alcohol use, alcohol problems, characteristics of their alcohol-related incident, reactions to the incident, attributions about the incident, and motivation to change drinking and heavy drinking. Path and regression analyses were used to identify the individual and incident-related characteristics that were related to motivation to change. Results Perceived aversiveness of the incident was directly and positively related to motivation to change drinking and heavy drinking. Alcohol consumption in the month before the incident and past-year alcohol problems were negatively related to motivation to change heavy drinking, and women were more motivated to change heavy drinking than men. The more students consumed in the incident, the more likely they were to feel responsible for it, and the more responsible they felt about the incident, the greater its aversiveness. Conclusions Individual and incident-related characteristics are both directly and indirectly associated with motivation to change following an alcohol-related incident, and therefore have implications for interventions with college drinkers who have experienced an alcohol-related incident. PMID:16847545
Gundling, F; Schepp, W
Malnutrition is very common in patients with liver cirrhosis and includes especially protein-calorie malnutrition. The pathophysiological reasons vary and are caused by metabolic modifications and characteristics of enteral absorption and digestion cause by the cirrhosis. Malnutrition contributes to overall mortality and complication rate of the chronic liver disease. An adequate daily energy and protein supply should be ensured in patients with liver cirrhosis, which is higher than that in the normal population, because of higher amino-acid turnover. Ascites may benefit from daily low-salt fluid intake. Nutritional substitution of vitamins and trace elements is indicated when symptoms of deficiency occur.
Pinter, Matthias; Trauner, Michael; Peck-Radosavljevic, Markus; Sieghart, Wolfgang
Liver cirrhosis, the end-stage of every chronic liver disease, is not only the major risk factor for the development of hepatocellular carcinoma but also a limiting factor for anticancer therapy of liver and non-hepatic malignancies. Liver cirrhosis may limit surgical and interventional approaches to cancer treatment, influence pharmacokinetics of anticancer drugs, increase side effects of chemotherapy, render patients susceptible for hepatotoxicity, and ultimately result in a competitive risk for morbidity and mortality. In this review, we provide a concise overview about the impact of liver cirrhosis on the management and prognosis of patients with primary liver cancer or non-hepatic malignancies. PMID:27843598
Juran, Brian D.; Lazaridis, Konstantinos N.
The etiology of the autoimmune liver disease primary biliary cirrhosis (PBC) remains largely unresolved, owing in large part to the complexity of interaction between environmental and genetic contributors underlying disease development. Observations of disease clustering, differences in geographical prevalence, and seasonality of diagnosis rates suggest the environmental component to PBC is strong, and epidemiological studies have consistently found cigarette smoking and history of urinary tract infection to be associated with PBC. Current evidence implicates molecular mimicry as a primary mechanism driving loss of tolerance and subsequent autoimmunity in PBC, yet other environmentally influenced disease processes are likely to be involved in pathogenesis. In this review, the authors provide an overview of current findings and touch on potential mechanisms behind the environmental component of PBC. PMID:25057950
Although ursodeoxycholic acid remains the only approved pharmacotherapy for patients with primary biliary cirrhosis, the better characterization of factors responsible for the poor response to this drug and the emergence of several new putative therapeutic targets now offer significant opportunities to improve the management of patients and our capacity to treat them more efficiently. The availability of novel treatment options, such as fibrates, budesonide, and obeticholic acid, all capable of improving prognostic markers, invites us to reconsider our management and treatment strategies. Early identification of high-risk patients should remain a priority to deliver adjunctive therapies to appropriately selected populations and increase their chances of success. Given the absence of comparative trials, the choice between second-line treatments should be dictated by the biochemical, histological, and expected tolerance profiles. Here the author presents a brief overview of what should be known in this field and proposes a practical approach to facilitate decision making.
Rodriguez-Roisin, R; Pares, A; Bruguera, M; Coll, J; Picado, C; Agusti-Vidal, A; Burgos, F; Rodes, J
The association of pulmonary fibrosis and primary biliary cirrhosis (PBC) remains controversial. To determine the frequency of pulmonary fibrosis in PBC, a carefully selected series of 14 PBC patients, seven patients with Sicca complex, and 14 control subjects have been studied. Seven of the 14 patients with PBC had Sjögren's syndrome, four of whom had some clinical evidence of pulmonary disease. Evaluation of ventilatory capacity, gas transfer factor, arterial blood gases, and lung mechanics were performed. Gas transfer was reduced in patients with PBC associated with Sjögen's syndrome and in patients with the Sicca complex. These results suggest that the respiratory, clinical, ad functional abnormalities found in PBC are related to the presence of an associated Sjögen's syndrome. PMID:7281088
Hernández-Boluda, J C; Jiménez, M; Rosiñol, L; Cervantes, F
A patient with primary biliary cirrhosis (PBC) who developed idiopathic myelofibrosis (IM) is reported. The initial diagnosis of PBC was established by liver biopsy, performed after a 2-month history of constitutional symptoms associated with abnormalities of the serum liver enzymes, with typical serum immunological markers being found. Although a favorable response of PBC to prednisone was observed, one and a half year later the patient developed anemia with anisocytosis and poikilocytosis, tear-drop cells, and leukoerythroblastic picture, and IM was diagnosed by bone marrow biopsy. A few months later, a rapid worsening of the patient's clinical condition was noted, with an increase in the constitutional symptoms and need for frequent packed RBC transfusions, and she finally died from an infectious complication. This case represents a new association of IM with an autoimmune disease, supporting the hypothesis of a possible immune basis of IM in some cases.
Sundström, M; Jones, A W; Ojanperä, I
Use and abuse of alcohol are common findings when unnatural deaths are investigated as evidenced by high blood- and urine- alcohol concentrations (BAC and UAC) at autopsy. Because ethanol is metabolized in the liver until the time of death, the autopsy BAC or UAC might be negative even though the deceased had consumed alcohol in the immediate ante-mortem period. Analysis of the non-oxidative metabolite of ethanol [ethyl glucuronide (EtG)] offers a more sensitive test of recent drinking. In this paper, we determined the concentrations of ethanol and EtG in urine samples from 972 consecutive forensic autopsies. In 425 cases (44%) both EtG and ethanol were positive, which supports ante-mortem drinking. In 342 cases (35%), both EtG and ethanol was negative, which speaks against any consumption of alcohol just before death. In 181 cases, ethanol was negative in urine (<0.2 g/kg), whereas EtG was positive (>0.5 mg/L), which points towards ingestion of alcohol some time before death. In these cases, mean and median concentrations of EtG were 53.2 mg/L and 23.7 mg/L, respectively, although there was no mention of alcohol on 131 of the death certificates. Alcohol was mentioned on death certificates as an underlying or immediate cause of death or a contributing factor in 435 (45%) cases, which rose to 566 (58%) cases when positive EtG results were included. This article demonstrates the usefulness of EtG analysis in routine post-mortem toxicology when ante-mortem drinking and alcohol-related deaths are investigated.
Kapoor, M; Chou, Y-L; Edenberg, H J; Foroud, T; Martin, N G; Madden, P A F; Wang, J C; Bertelsen, S; Wetherill, L; Brooks, A; Chan, G; Hesselbrock, V; Kuperman, S; Medland, S E; Montgomery, G; Tischfield, J; Whitfield, J B; Bierut, L J; Heath, A C; Bucholz, K K; Goate, A M; Agrawal, A
Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples—the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement. PMID:27003187
Ward, Janice; Robinson, Philip J
Cirrhosis predisposes to hepatocellular carcinoma (HCC) which develops by sequential steps of de-differentiation of hepatocytes from regenerative nodules via borderline (dysplastic) nodules to frankly malignant HCC. Effective treatment depends on early recognition of HCC, so the key tasks for imaging are firstly recognising the presence of a suspicious lesion, and secondly differentiating between benign, borderline and malignant nodules. Screening of high-risk cirrhotic patients with sonography and measurement of alpha fetoprotein (AFP) is helpful but will not reliably differentiate small HCC from benign or dysplastic nodules. Large HCCs can usually be recognised by their characteristic morphology on imaging, but the appearances of smaller benign and malignant nodules show considerable overlap on unenhanced sonography, CT and MRI. Increasing degrees of histological malignancy are associated with increasing arterialisation and loss of portal blood supply, so the recognition of HCC requires the use of dynamic imaging with contrast-enhanced CT or T1-weighted MRI with gadolinium enhancement. Sonography with microbubble contrast media now offers another method for detecting arterialised nodules; however, some non-malignant nodules show arterial hypervascularity and a minority of HCCs are hypovascular, so the assessment of perfusion does not conclusively distinguish benign from malignant lesions. Kupffer cell function is another attribute of liver tissue which can be explored using MRI with superparamagnetic iron oxide particles (SPIO). Experience thus far suggests that uptake of SPIO is an effective discriminator between benign and malignant nodules. The combination of SPIO with gadolinium-enhanced MRI offers the opportunity for imaging characterisation of cirrhotic nodules by cellular function as well as by blood supply, and this approach is now proposed as the examination of choice for detecting HCC in cirrhosis.
McPherson, Stuart; Dyson, Jessica; Austin, Andrew; Hudson, Mark
Recently, there has been a significant increase in the prevalence of chronic liver disease in the UK, and as a result, hospital admissions and deaths due to liver disease have also increased. The 2013 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) of patients with alcohol-related liver disease (ARLD) found that less than half the number of patients who died from ARLD received 'good care', and avoidable deaths were identified. In order to improve the care of patients admitted with ARLD, the NCEPOD report recommended that a 'toolkit' for the acute management of patients admitted with decompensated ARLD be developed and made widely available. As a result, we have developed a 'care bundle' for patients admitted with decompensated cirrhosis (of all aetiologies) to ensure that effective evidence-based treatments are delivered within the first 24 h. This care bundle provides a checklist to ensure that all appropriate investigations are undertaken when a patient with decompensated cirrhosis presents and provides clinicians with clear guidance on the initial management of alcohol withdrawal, infection, acute kidney injury, gastrointestinal bleeding and encephalopathy. The first 24 h are particularly important, as early intervention can reduce mortality and shorten hospital stay, and specialist gastroenterology/liver advice is not always available during this period. This review will discuss the care bundle and the evidence base behind the treatment recommendations made.
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Xue, Ran; Meng, Qinghua; Li, Juan; Feng, Jiliang; Shi, Hanping
Hepatocellular carcinoma (HCC) accounts for about 90% of all malignant tumors of liver, ranking fifth in the worldwide incidence of malignant tumors and the third in fatality. More and more evidences suggest that cancer is a metabolic-related disease. From the analysis of recent clinical research data, we found that as the severity of the cirrhosis aggravated, patients with HCC and end-stage liver cirrhosis had a flat energy metabolism which was better than it in patients with simple end-stage liver cirrhosis. Based on these clinical phenomenon, the major aim of this study is to present a new hypothesis: "compensated liver function mechanism" for patients with HCC and liver cirrhosis, cancer cells may play a role to compensate liver function. In this study, we elaborated relevant content about this novel standpoint combined with tumor energy metabolism reprogramming mechanism and tumor cell origin as well as cell exchange mechanism.
Khan, Ali S; Eloubeidi, Mohamad A; Khashab, Mouen A
Treatment of choledocholithiasis and cholelithiasis in patients with cirrhosis often requires diagnostic and therapeutic endoscopy such as endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). Patients with underlying cirrhosis may have coagulopathy, hepatic encephalopathy, ascites and other comorbidities associated with cirrhosis that can make endoscopic therapy challenging and can be associated with a higher risk of adverse events. Given the unique derangements of physiologic parameters associated with cirrhosis this population requires a truly multifaceted and multidisciplinary understanding between therapeutic endoscopists, hepatologists and anesthesiologists. For therapeutic endoscopists, it is critical to be aware of the specific issues unique to this population of patients to optimize outcomes and avoid adverse events. The epidemiology of gallstone disease, the diagnostic and therapeutic approach to patients with varying degree of hepatic dysfunction, and a review of the available literature in this area are presented.
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Qamar, Amir A
With the growing epidemic of obesity, the incidence of both nonalcoholic fatty liver disease (NAFL) and nonalcoholic steatohepatitis (NASH) is increasing. The intestinal microbiota differs between individuals who are obese or have normal body mass indices. Animal studies have shown increased intestinal permeability in NAFL, NASH, and cirrhosis. This increases the risk of oxidative and inflammatory injury to the liver from intestinal microbacteria. It may also increase the risk of fatty acid injury and fatty deposition. Bacterial translocation is associated with increased portal hypertension and hepatic encephalopathy in cirrhosis. By preventing bacterial adhesion and translocation, probiotics may have a role in the management of patients with NAFL, NASH, and cirrhosis. Multiple small studies have suggested that probiotics improve some of the clinical markers of activity in patients with NAFL and NASH. Controlled studies have also shown improved outcomes in patients with cirrhosis who were treated with probiotics.
Hughes, P.; McGavin, C. R.
In a small number of cases the co-existence of primary biliary cirrhosis and sarcoidosis is assumed from clinical serological and histological findings. A case of sarcoidosis is reported in which the M2 antibody, a highly specific marker for primary biliary cirrhosis, was detected. The patient also developed a severe myositis and a possible overlap syndrome is discussed. PMID:9059489
Mathur, Amit K; Chakrabarti, Apurba K; Mellinger, Jessica L; Volk, Michael L; Day, Ryan; Singer, Andrew L; Hewitt, Winston R; Reddy, Kunam S; Moss, Adyr A
AIM To determine whether hospital characteristics predict cirrhosis mortality and how much variation in mortality is attributable to hospital differences. METHODS We used data from the 2005-2011 Nationwide Inpatient Sample and the American Hospital Association Annual survey to identify hospitalizations for decompensated cirrhosis and corresponding facility characteristics. We created hospital-specific risk and reliability-adjusted odds ratios for cirrhosis mortality, and evaluated patient and facility differences based on hospital performance quintiles. We used hierarchical regression models to determine the effect of these factors on mortality. RESULTS Seventy-two thousand seven hundred and thirty-three cirrhosis admissions were evaluated in 805 hospitals. Hospital mean cirrhosis annual case volume was 90.4 (range 25-828). Overall hospital cirrhosis mortality rate was 8.00%. Hospital-adjusted odds ratios (aOR) for mortality ranged from 0.48 to 1.89. Patient characteristics varied significantly by hospital aOR for mortality. Length of stay averaged 6.0 ± 1.6 days, and varied significantly by hospital performance (P < 0.001). Facility level predictors of risk-adjusted mortality were higher Medicaid case-mix (OR = 1.00, P = 0.029) and LPN staffing (OR = 1.02, P = 0.015). Higher cirrhosis volume (OR = 0.99, P = 0.025) and liver transplant program status (OR = 0.83, P = 0.026) were significantly associated with survival. After adjusting for patient differences, era, and clustering effects, 15.3% of variation between hospitals was attributable to differences in facility characteristics. CONCLUSION Hospital characteristics account for a significant proportion of variation in cirrhosis mortality. These findings have several implications for patients, providers, and health care delivery in liver disease care and inpatient health care design. PMID:28348492
Objectives: Studies suggest that periodontal disease, a source of subclinical and persistent infection, may be associated with various systemic conditions, including liver cirrhosis. The aim of this study was to examine the literature and determine the relationship between periodontal disease and liver cirrhosis and to identify opportunities and directions for future research in this area. Methods: A systematic review of English articles in the PubMed, EMBASE, and Scopus databases was conducted using search terms including ‘liver cirrhosis’, ‘end-stage liver disease’, ‘liver diseases’, ‘oral health’, ‘periodontal disease’, ‘mouth disease’, ‘gingivitis’, and ‘periodontitis’. Results: Thirteen studies published between 1981 and 2014 were found to include data on oral health and periodontal disease in cirrhotic patients. Studies indicated an increased incidence of periodontal disease in patients with liver cirrhosis, measured with several different periodontal indices. The reported prevalence of periodontal disease in cirrhosis patients ranged from 25.0% to 68.75% in four studies and apical periodontitis was found in 49%–79% of the patients. One study found that mortality was lower among patients who underwent dental treatment versus non-treated patients. Another study suggested an association between periodontal disease and the progression of liver cirrhosis, but data are sparse and conflicting as to whether periodontal disease is correlated to cirrhosis aetiology and severity. Conclusion: Despite the clinical reality of periodontal disease in liver cirrhosis patients, there are few published studies. Before clinical implications can be addressed, more data on the prevalence of and correlation between periodontal disease and liver cirrhosis aetiology, duration, and progression are needed. PMID:26770799
Frøkjaer, Vibe G; Strauss, Gitte I; Mehlsen, Jesper; Knudsen, Gitte M; Rasmussen, Verner; Larsen, Fin S
Cerebral blood flow autoregulation is lost in patients with severe liver cirrhosis. The cause of this is unknown. We determined whether autonomic dysfunction was related to impaired cerebral autoregulation in patients with cirrhosis. Fourteen patients with liver cirrhosis and 11 healthy volunteers were recruited. Autonomic function was assessed in response to deep breathing, head-up tilt and during 24-h Holter monitoring. Cerebral autoregulation was assessed by determining the change in mean cerebral blood flow velocity (MCAVm, transcranial Doppler) during an increase in blood pressure induced by norepinephrine infusion (NE). The severity of liver disease was assessed using the Child-Pugh scale (class A, mild; class B, moderate; class C, severe liver dysfunction).NE increased blood pressure similarly in the controls (27 (24-32) mmHg) and patients with the most severe liver cirrhosis (Child-Pugh C, 31 (26-44) mmHg, p=0.405 Mann-Whitney). However, the increase in MCAVm was greater in cirrhosis patients compared to the controls (Child-Pugh C, 26 (24-39) %; controls, 3 (-1.3 to 3) %; respectively, p=0.016, Mann-Whitney). HRV during deep breathing was reduced in the cirrhosis patients (Child-Pugh C, 6.0+/-2.0 bpm) compared to the controls (21.7+/-2.2 bpm, p=0.001, Tukey' test). Systolic blood pressure fell during head-up tilt only in patients with severe cirrhosis. Our results imply that cerebral autoregulation was impaired in the most severe cases of liver cirrhosis, and that those with impaired cerebral autoregulation also had severe parasympathetic and sympathetic autonomic dysfunction. Furthermore, the degree of liver dysfunction was associated with increasing severity of autonomic dysfunction. Although this association is not necessarily causal, we postulate that the loss of sympathetic innervation to the cerebral resistance vessels may contribute to the impairment of cerebral autoregulation in patients with end-stage liver disease.
Larimer, Mary E; Turner, Aaron P; Mallett, Kimberly A; Geisner, Irene Markman
The authors examined the relation between Greek students' perceptions of alcohol consumption in their pledge classes (descriptive norms) and acceptability of drinking (injunctive norms) and the ability of these normative influences to predict drinking behavior, alcohol-related negative consequences, and symptoms of alcohol dependence concurrently and prospectively over 1 year. Participants were 279 men and 303 women recruited from incoming pledge classes of 12 fraternities and 6 sororities, who completed measures of descriptive and injunctive norms, alcohol use, and consequences. Results revealed that descriptive norms significantly predicted concurrent drinking. After controlling for baseline drinking, injunctive norms significantly predicted drinking 1 year later and predicted alcohol-related consequences and dependency symptoms at baseline and follow-up. The potential to incorporate injunctive norms into preventive interventions is discussed.
Larimer, Mary E.; Turner, Aaron P.; Mallett, Kimberly A.; Geisner, Irene Markman
The authors examined the relation between Greek students’ perceptions of alcohol consumption in their pledge classes (descriptive norms) and acceptability of drinking (injunctive norms) and the ability of these normative influences to predict drinking behavior, alcohol-related negative consequences, and symptoms of alcohol dependence concurrently and prospectively over 1 year. Participants were 279 men and 303 women recruited from incoming pledge classes of 12 fraternities and 6 sororities, who completed measures of descriptive and injunctive norms, alcohol use, and consequences. Results revealed that descriptive norms significantly predicted concurrent drinking. After controlling for baseline drinking, injunctive norms significantly predicted drinking 1 year later and predicted alcohol-related consequences and dependency symptoms at baseline and follow-up. The potential to incorporate injunctive norms into preventive interventions is discussed. PMID:15482075
Krzyżanowska, Patrycja; Drzymała-Czyż, Sławomira; Pogorzelski, Andrzej; Duś-Żuchowska, Monika; Skorupa, Wojciech; Bober, Lyudmyla; Sapiejka, Ewa; Oralewska, Beata; Rohovyk, Nataliya; Moczko, Jerzy; Nowak, Jan; Wenska-Chyży, Ewa; Rachel, Marta; Lisowska, Aleksandra; Walkowiak, Jarosław
The available data on the influence of liver cirrhosis on vitamin K status in CF patients is scarce. Therefore, the aims of the present study were to assess the prevalence of vitamin K deficiency in cirrhotic CF subjects and to determine whether it correlates with liver cirrhosis. The study group comprised of 27 CF patients with and 63 without liver cirrhosis. Vitamin K status was assessed using prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). PIVKA-II concentrations were higher in cirrhotic than in non-cirrhotic CF patients (median [1st-3rd quartile]: 3.2ng/ml [1.0-10.0] vs. 1.3ng/ml [0.2-2.6], p=0.0029). However, the differences in u-OC percentages between the studied groups did not reach the level of significance (49.4% [7.0-73.8] vs. 8.0% [2.6-59.1], p=0.0501). Based on multiple linear regression analysis the dose of vitamin K and F508del mutation were potentially defined as determinants of vitamin K deficiency. Liver cirrhosis was not documented to be an independent risk factor. In CF patients with liver cirrhosis vitamin K deficiency is not only more frequent, but also more severe. However, not liver cirrhosis, but the presence of a F508del CFTR mutation constitutes an independent risk factor for vitamin K deficiency.
de la Garza, Rocio G; Morales-Garza, Luis Alonso; Martin-Estal, Irene; Castilla-Cortazar, Inma
Cirrhosis represents the final stage of chronic liver damage, which can be due to different factors such as alcohol, metabolic syndrome with liver steatosis, autoimmune diseases, drugs, toxins, and viral infection, among others. Nowadays, cirrhosis is an important health problem and it is an increasing cause of morbidity and mortality, being the 14th most common cause of death worldwide. The physiopathological pathways that lead to fibrosis and finally cirrhosis partly depend on the etiology. Nevertheless, some common features are shared in this complex mechanism. Recently, it has been demonstrated that cirrhosis is a dynamic process that can be altered in order to delay or revert fibrosis. In addition, when cirrhosis has been established, insulin-like growth factor-1 (IGF-1) deficiency or reduced availability is a common condition, independently of the etiology of chronic liver damage that leads to cirrhosis. IGF-1 deprivation seriously contributes to the progressive malnutrition of cirrhotic patient, increasing the vulnerability of the liver to establish an inflammatory and oxidative microenvironment with mitochondrial dysfunction. In this context, IGF-1 deficiency in cirrhotic patients can justify some of the common characteristics of these individuals. Several studies in animals and humans have been done in order to test the replacement of IGF-1 as a possible therapeutic option, with promising results.
Sun, Shan; Song, Zhenyuan; Cotler, Scott J; Cho, Michael
Cirrhosis is a life-threatening condition that is generally attributed to overproduction of collagen fibers in the extracellular matrix that mechanically stiffens the liver. Chronic liver injury due to causes including viral hepatitis, inherited and metabolic liver diseases and external factors such as alcohol abuse can result in the development of cirrhosis. Progression of cirrhosis leads to hepatocellular dysfunction. While extensive studies to understand the complexity underlying liver fibrosis have led to potential application of anti-fibrotic drugs, no such FDA-approved drugs are currently available. Additional studies of hepatic fibrogenesis and cirrhosis primarily have focused on the extracellular matrix, while hepatocyte biomechanics has received limited attention. The role of hepatocyte biomechanics in liver cirrhosis remains elusive, and how the cell stiffness is correlated with biological functions of hepatocytes is also unknown. In this study, we demonstrate that the biomechanical properties of hepatocytes are correlated with their functions (e.g., glucose metabolism), and that hepatic dysfunction can be restored through modulation of the cellular biomechanics. Furthermore, our results indicate the hepatocyte functionality appears to be regulated through a crosstalk between the Rho and Akt signaling. These novel findings may lead to biomechanical intervention of hepatocytes and the development of innovative tissue engineering for clinical treatment to target liver cells rather than exclusively focusing on the extracellular matrix alone in liver cirrhosis.
Wang, Ji Yao
Antiviral therapy is important in patients with hepatitis B virus (HBV)-related decompensated cirrhosis. This therapy is beneficial in most patients for the stabilization or improvement of liver disease; however, advanced cirrhosis with a high Child-Pugh or model for end-stage liver disease (MELD) score may have progressed and does not benefit from antiviral therapy. It is important to identify patients with severe decompensated cirrhosis who will not improve under antiviral therapy and who require liver transplantation as early as possible. Entecavir (ETV) or tenofovir disoproxil fumarate (TDF) is the first-line therapy for nucleos(t)ide analogue (NA)-naive patients with decompensated cirrhosis due to their potent and prompt HBV suppressive effect and low rate of drug-resistant mutations. Patients on antiviral therapy should be monitored for virological and clinical response, compliance, drug resistance and adverse effects as well as surveillance for hepatocellular carcinoma (HCC). Additional studies of TDF and ETV are necessary to determine the optimal agent(s) for treating naive patients and those with drug-resistant decompensated cirrhosis. In order to evaluate the effectiveness of NA for the treatment of decompensated cirrhotic patients in the real world, high quality observational studies such as registration studies of antiviral therapy for HBV-related cirrhosis and a long-term follow-up in China, where a large number of such patients are found, are recommended.
de la Garza, Rocio G.; Morales-Garza, Luis Alonso; Martin-Estal, Irene; Castilla-Cortazar, Inma
Cirrhosis represents the final stage of chronic liver damage, which can be due to different factors such as alcohol, metabolic syndrome with liver steatosis, autoimmune diseases, drugs, toxins, and viral infection, among others. Nowadays, cirrhosis is an important health problem and it is an increasing cause of morbidity and mortality, being the 14th most common cause of death worldwide. The physiopathological pathways that lead to fibrosis and finally cirrhosis partly depend on the etiology. Nevertheless, some common features are shared in this complex mechanism. Recently, it has been demonstrated that cirrhosis is a dynamic process that can be altered in order to delay or revert fibrosis. In addition, when cirrhosis has been established, insulin-like growth factor-1 (IGF-1) deficiency or reduced availability is a common condition, independently of the etiology of chronic liver damage that leads to cirrhosis. IGF-1 deprivation seriously contributes to the progressive malnutrition of cirrhotic patient, increasing the vulnerability of the liver to establish an inflammatory and oxidative microenvironment with mitochondrial dysfunction. In this context, IGF-1 deficiency in cirrhotic patients can justify some of the common characteristics of these individuals. Several studies in animals and humans have been done in order to test the replacement of IGF-1 as a possible therapeutic option, with promising results. PMID:28270882
Harding, Damian J; Perera, M Thamara PR; Chen, Frederick; Olliff, Simon; Tripathi, Dhiraj
Portal vein thrombosis (PVT) is encountered in liver cirrhosis, particularly in advanced disease. It has been a feared complication of cirrhosis, attributed to significant worsening of liver disease, poorer clinical outcomes and potential inoperability at liver transplantation; also catastrophic events such as acute intestinal ischaemia. Optimal management of PVT has not yet been addressed in any consensus publication. We review current literature on PVT in cirrhosis; its prevalence, pathophysiology, diagnosis, impact on the natural history of cirrhosis and liver transplantation, and management. Studies were identified by a search strategy using MEDLINE and Google Scholar. The incidence of PVT increases with increasing severity of liver disease: less than 1% in well-compensated cirrhosis, 7.4%-16% in advanced cirrhosis. Prevalence in patients undergoing liver transplantation is 5%-16%. PVT frequently regresses instead of uniform thrombus progression. PVT is not associated with increased risk of mortality. Optimal management has not been addressed in any consensus publication. We propose areas for future research to address unresolved clinical questions. PMID:26078553
Kumar, K. V. S. Hari; Pawah, A. K.; Manrai, Manish
Background: Liver dysfunction leads to endocrine disturbance due to the alteration in protein metabolism or synthesis. We studied the presence of occult endocrine dysfunction in liver cirrhosis and compared the same with underlying etiology. Materials and Methods: We evaluated thirty patients with liver cirrhosis in this cross-sectional, observational study. All subjects were assessed for pituitary, thyroid, adrenal, and gonadal function. The patients were divided into Group 1 (cirrhosis, n = 30) and Group 2 (controls, n = 15) and the data were analyzed with appropriate statistical tests. Results: The study participants (20 males, 10 females) had a mean age of 54.5 ± 12.4 years and duration of the cirrhosis 5.1 ± 2.7 years. Four patients were in Child Class A, 11 and 15 patients were in Child Classes B and C, respectively. Eleven out of thirty patients (37%) had endocrine disorders, that include subclinical hypothyroidism (n = 3), primary hypothyroidism (n = 1), Sick Euthyroid syndrome (n = 3), central hypothyroidism (n = 2), secondary hypogonadism (n = 3) and growth hormone deficiency in three patients. Two patients had partial hypopituitarism and one patient had complete hypopituitarism. Conclusion: Occult endocrine dysfunction of thyroid and gonadal axes is common in patients with cirrhosis of the liver. The hormonal abnormalities are not different based on the etiology of the cirrhosis. PMID:28217586
Satishchandran, Abhishek; Iracheta-Vellve, Arvin; Ambade, Aditya; Kodys, Karen; Catalano, Donna; Ward, Doyle V.; Szabo, Gyongyi
Background Alcohol-induced intestinal dysbiosis disrupts homeostatic gut-liver axis function and is essential in the development of alcoholic liver disease. Here, we investigate changes in enteric microbiome composition in a model of early alcoholic steatohepatitis and dissect the pathogenic role of intestinal microbes in alcohol-induced liver pathology. Materials and methods Wild type mice received a 10-day diet that was either 5% alcohol-containing or an isocaloric control diet plus a single binge. 16S rDNA sequencing defined the bacterial communities in the cecum of alcohol- and pair-fed animals. Some mice were treated with an antibiotic cocktail prior to and throughout alcohol feeding. Liver neutrophils, cytokines and steatosis were evaluated. Results Acute-on-chronic alcohol administration induced shifts in various bacterial phyla in the cecum, including increased Actinobacteria and a reduction in Verrucomicrobia driven entirely by a reduction in the genus Akkermansia. Antibiotic treatment reduced the gut bacterial load and circulating bacterial wall component lipopolysaccharide (LPS). We found that bacterial load suppression prevented alcohol-related increases in the number of myeloperoxidase- (MPO) positive infiltrating neutrophils in the liver. Expression of liver mRNA tumor necrosis factor alpha (Tnfα), C-X-C motif chemokine ligand 1 (Cxcl1) and circulating protein monocyte chemoattractant protein-1 (MCP-1) were also reduced in antibiotic-treated alcohol-fed mice. Alcohol-induced hepatic steatosis measured by Oil-Red O staining was significantly reduced in antibiotic treated mice. Genes regulating lipid production and storage were also altered by alcohol and antibiotic treatment. Interestingly, antibiotic treatment did not protect from alcohol-induced increases in serum aminotransferases (ALT/AST). Conclusions Our data indicate that acute-on-chronic alcohol feeding alters the microflora at multiple taxonomic levels and identifies loss of Akkermansia as an
Primack, Brian A.; McClure, Auden; Li, Zhigang; Sargent, James D.
Background The average U.S. adolescent is exposed to about 2.5 hours of popular music per day and 8 mentions of alcohol brands every day. Alcohol brand mentions may function as advertising whether or not they are sanctioned by the alcohol industry. Our study aimed to determine associations between adolescents' involvement with music containing alcohol brand mentions and alcohol-related behaviors. Methods In 2010–2011 we conducted a random-digit-dial survey using national U.S. land line and cell phone frames. Through screening interviews, we identified 6,466 eligible households with subjects between 15 to 23 years of age, of whom 3422 (52%) completed the telephone survey. Of these, 2541 opted to participate in a subsequent Web-based component. Independent variables included a composite score indicating owning and liking popular songs with alcohol brand mentions and correct recall of alcohol brands in songs. Outcome measures included ever having consumed a complete drink, ever bingeing, bingeing at least monthly, and having experienced problems from alcohol use. Results Among the 2541 participants, compared with those in the lowest tertile on the receptivity scale, those in the highest tertile had higher odds of having had a complete drink (OR=3.4; 95% CI=2.2, 5.2) after adjusting for age, sex, race/ethnicity, socioeconomic status, sensation seeking, friend alcohol use, and parent alcohol use. Compared with those who did not identify at least one alcohol brand correctly, those who did had over twice the odds of having had a complete drink (OR=2.1; 95% CI=1.2, 3.8) after adjusting for all covariates. Results were also significant for the outcome of ever bingeing but not for bingeing at least monthly or having had problems due to drinking. Conclusions In a national sample of U.S. adolescents and young adults, there were independent associations between involvement with popular music containing alcohol brand mentions and both having ever had a complete drink and
Brooks, Alyssa T; Wallen, Gwenyth R
Sleep disturbances are common among alcohol-dependent individuals and are often associated with relapse. The utility of behavioral therapies for sleep disturbances, including cognitive-behavioral therapy for insomnia (CBT-I), among those with alcohol-related disorders is not well understood. This review systematically evaluates the evidence of CBT-I and related behavioral therapies applied to those with alcohol-related disorders and accompanying sleep disturbances. A search of four research databases (PubMed, PsycINFO, Embase, and CINAHL Plus) yielded six studies that met selection criteria. Articles were reviewed using Cochrane’s Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) scoring system. A majority of the studies demonstrated significant improvements in sleep efficiency among behavioral therapy treatment group(s), including but not limited to CBT-I. While behavioral sleep interventions have been successful in varied populations, they may not be utilized to their full potential among those with alcohol-related disorders as evidenced by the low number of studies found. These findings suggest a need for mixed-methods research on individuals’ sleep experience to inform interventions that are acceptable to the target population. PMID:25288884
Frahm, Kathryn A; Barnett, Scott D; Brown, Lisa M; Hickling, Edward J; Olney, Ron; Campbell, Robert R; Lapcevic, William A
The purpose of this study was to document preliminary findings of the association between posttraumatic stress disorder (PTSD), mental health service use, and alcohol related health visits among veterans following 2004-2005 Florida hurricane seasons. A retrospective review of the Veterans Health Administration Medical SAS Outpatient Dataset was conducted to identify veterans residing in Florida during the 2004-2005 hurricane seasons with a history of PTSD and/or PTSD and a substance use disorder. It was found that veterans with PTSD residing in counties affected by hurricanes demonstrated an immediate 28 % increase in use of mental health services following hurricane landfall versus veterans residing in non-hurricane affected counties (+28.0 vs. -6.5 %, p = 0.001). Additionally, veterans residing in affected counties were found to use more group psychotherapy treatment sessions overall (30.3 vs. 27.2 %, p = 0.001). Of note, veterans with PTSD experienced a -0.16 per month (p = 0.114) decrease in alcohol related visits following the 2004 hurricane season. These findings provide insight into the mental health needs of veterans with PTSD following a disaster and can inform delivery of services to veterans with PTSD and alcohol related issues in disaster prone areas.
Bakhshi, Savita; While, Alison E.
Health professionals’ personal health behaviors have been found to be associated with their practices with patients in areas such as smoking, physical activity and weight management, but little is known in relation to alcohol use. This review has two related strands and aims to: (1) examine health professionals’ alcohol-related health promotion practices; and (2) explore the relationship between health professionals’ personal alcohol attitudes and behaviors, and their professional alcohol-related health promotion practices. A comprehensive literature search of the Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, British Nursing Index, Web of Science, Scopus and Science Direct (2007–2013) identified 26 studies that met the inclusion criteria for Strand 1, out of which six were analyzed for Strand 2. The findings indicate that health professionals use a range of methods to aid patients who are high-risk alcohol users. Positive associations were reported between health professionals’ alcohol-related health promotion activities and their personal attitudes towards alcohol (n = 2), and their personal alcohol use (n = 2). The findings have some important implications for professional education. Future research should focus on conducting well-designed studies with larger samples to enable us to draw firm conclusions and develop the evidence base. PMID:24366045
Johnson, Sean J; Alford, Chris; Stewart, Karina; Verster, Joris C
Previous research reported positive associations between alcohol mixed with energy drink (AMED) consumption and overall alcohol consumption. However, results were largely based on between-subjects comparisons comparing AMED consumers with alcohol-only (AO) consumers, and therefore cannot sufficiently control for differences in personal characteristics between these groups. In order to determine whether AMED consumers drink more alcohol on occasions they consume AMED compared to those when they drink AO additional within-subjects comparisons are required. Therefore, this UK student survey assessed both alcohol consumption and alcohol-related negative consequences when consumed alone and when mixed with energy drinks, using a within-subject design. A total of 1873 students completed the survey, including 732 who consumed AMED. It was found that AMED consumers drank significantly less alcohol when they consumed AMED compared to when they drank AO (p < 0.001). In line with reduced alcohol consumption significantly fewer negative alcohol-related consequences were reported on AMED occasions compared to AO occasions (p < 0.001). These findings suggest that mixing alcohol with energy drinks does not increase total alcohol consumption or alcohol-related negative consequences.
Broitman, Selwyn A.; Gottlieb, Leonard S.; Zamcheck, Norman
Two groups of adult rats fed a choline-deficient diet supplemented with neomycin in their drinking water for 250 or 350 days were protected against the development of liver fibrosis and cirrhosis. At the termination of the study these animals weighed more than others not receiving neomycin. This difference in weight did not appear to be caused by a growth-promoting effect of neomycin but rather reflected the increased severity of liver disease and a resultant weight loss in animals not receiving neomycin. Protection by neomycin was cancelled when Salmonella typhosa endotoxin was added to the drinking water. It was concluded that the protective effect of neomycin was mediated by an alteration in the intestinal microflora resulting in a reduction in the numbers of organisms contributing to intraluminal endotoxin. In the presence of choline deficiency, absorption of intraluminal endotoxin may contribute to the development of fibrosis and cirrhosis. PMID:14151103
Artigas, Antonio; Wernerman, Jan; Arroyo, Vicente; Vincent, Jean-Louis; Levy, Mitchell
The metabolism of albumin in inflammatory states such as sepsis or major surgery is complex and still not well characterized. Nevertheless, in inflammatory states, albumin synthesis has been observed to increase. By contrast, in decompensated cirrhosis, a disease characterized by systemic inflammation, albumin synthesis by the liver may decrease to 30% to 50% of normal values. Furthermore, in these conditions, there are high capillary leakage and altered albumin kinetics. The discussion regarding the effect of exogenous albumin administration on intravascular volume in inflammatory states should therefore address albumin turnover. To add complexity to our understanding of the effects of albumin, there are many data indicating that the therapeutic action of albumin is mediated not only through the impact on plasma volume expansion but also through a modulatory effect on inflammation and oxidative stress. All these characteristics are relevant to diseases associated with systemic inflammation including sepsis and decompensated cirrhosis.
Webb, G J; Siminovitch, K A; Hirschfield, G M
Primary biliary cirrhosis (PBC), a classic autoimmune liver disease, is characterised by a progressive T cell predominant lymphocytic cholangitis, and a serologic pattern of reactivity in the form of specific anti-mitochondrial antibodies (AMA). CD4+ T cells are particularly implicated by PBC's cytokine signature, the presence of CD4+ T cells specific to mitochondrial auto-antigens, the expression of MHC II on injured biliary epithelial cells, and PBC's coincidence with other similar T cell mediated autoimmune conditions. CD4+ T cells are also central to current animal models of PBC, and their transfer typically also transfers disease. The importance of genetic risk to developing PBC is evidenced by a much higher concordance rate in monozygotic than dizygotic twins, increased AMA rates in asymptomatic relatives, and disproportionate rates of disease in siblings of PBC patients, PBC family members and certain genetically defined populations. Recently, high-throughput genetic studies have greatly expanded our understanding of the gene variants underpinning risk for PBC development, so linking genetics and immunology. Here we summarize genetic association data that has emerged from large scale genome-wide association studies and discuss the evidence for the potential functional significance of the individual genes and pathways identified; we particularly highlight associations in the IL-12-STAT4-Th1 pathway. HLA associations and epigenetic effects are specifically considered and individual variants are linked to clinical phenotypes where data exist. We also consider why there is a gap between calculated genetic risk and clinical data: so-called missing heritability, and how immunogenetic observations are being translated to novel therapies. Ultimately whilst genetic risk factors will only account for a proportion of disease risk, ongoing efforts to refine associations and understand biologic links to disease pathways are hoped to drive more rational therapy for
Selmi, Carlo; Lleo, Ana; Pasini, Simone; Zuin, Massimo; Gershwin, M Eric
There has been a rapid growth in our understanding of the molecular bases of primary biliary cirrhosis (PBC). These efforts were initiated when the immunodominant mitochondrial autoantigen was cloned and sequenced. Using the recombinant cloned antigen as a tool, research has focused on the effector mechanisms of disease and the uniqueness of the primary target tissue, the intrahepatic bile ducts. Most recently, there have been experimental data suggesting that innate immunity changes may be critical to the initiation and perpetuation of the autoimmune injury, as in the case of the enhanced response of monocytes and memory B cells to infectious stimulation and environmental mimics. These observations are important as they help fill in the many gaps which remain on the most difficult subject of autoimmunity, etiology. Indeed, based on the available data, several experimental models of PBC have been developed. These models illustrate and suggest that PBC can be initiated by several mechanisms, all of which lead to loss of tolerance to the mitochondrial antigens. However, once this adaptive response develops, it appears that much of the subsequent pathology is exacerbated by innate responses. We suggest that future therapeutic efforts in PBC will depend heavily on understanding the nature of this innate immune responses and methodology to blunt their cytotoxicity.
Gastroesophageal varices are a direct consequence of portal hypertension. Nonselective beta-adrenergic blockers decrease portal pressure and are effective in preventing variceal hemorrhage. However, a large multicenter placebo-controlled trial demonstrates that nonselective beta-adrenergic blockers are not effective in preventing the development of varices and are associated with a significant rate of adverse events. This therapy is, therefore, not recommended in compensated cirrhotic patients without varices at large. In this very compensated group of patients with cirrhosis (stage 1, ie, without varices and without ascites or encephalopathy) the predictive value (both for the development of varices and for the development of clinical decompensation) of a baseline hepatic venous pressure gradient greater than 10 mm Hg is confirmed, supporting this threshold level as one that defines a clinically significant portal hypertension. Importantly, reductions in hepatic venous pressure gradient >10% are associated with a significant reduction in the development of varices, a therapeutic goal that could be achieved through the use of beta-blockers or other drugs being developed for the treatment of portal hypertension.
Nishikawa, Hiroki; Osaki, Yukio
The liver is the major organ for the metabolism of three major nutrients: protein, fat, and carbohydrate. Chronic hepatitis C virus infection is the major cause of chronic liver disease. Liver cirrhosis (LC) results from different mechanisms of liver injury that lead to necroinflammation and fibrosis. LC has been seen to be not a single disease entity but one that can be graded into distinct clinical stages related to clinical outcome. Several noninvasive methods have been developed for assessing liver fibrosis and these methods have been used for predicting prognosis in patients with LC. On the other hand, subjects with LC often have protein-energy malnutrition (PEM) and poor physical activity. These conditions often result in sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictive factors for poorer survival in patients with LC. Based on these backgrounds, several methods for evaluating nutritional status in patients with chronic liver disease have been developed and they have been preferably used in the clinical field practice. In this review, we will summarize the current knowledge in the field of LC from the viewpoints of diagnostic method, nutritional status, and clinical outcomes.
Ojeda, Antonio; Moreno, Luis A
Pain management in patients with liver cirrhosis is a real challenge and is often inadequate due to a lack of therapeutic efficacy or the high incidence of adverse effects. The focus of treatment differs depending on whether the pain is acute or chronic and involves understanding the causative pathophysiological mechanism. Analgesics should be started with the minimum effective dose and should be titrated slowly with avoidance of polypharmacy. Adverse effects must be monitored, especially sedation and constipation, which predispose the patient to the development of hepatic encephalopathy. The first-line drug is paracetamol, which is safe at doses of 2-3g/day. Non-steroidal anti-inflammatory agents are contraindicated because they can cause acute renal failure and/or gastrointestinal bleeding. Tramadol is a safe option for moderate-severe pain. The opioids with the best safety profile are fentanyl and hydromorphone, with methadone as an alternative. Topical treatment can reduce oral drug consumption. In neuropathic pain the first-line therapeutic option is gabapentin. The use of antidepressants such as amitriptyline can be considered in some patients. Interventional techniques are a valuable tool in moderate to severe pain, since they allow a reduction in drug therapy and consequently its adverse effects. Psychological treatment, physical therapy and rehabilitation should be considered as part of multimodality therapy in the management of chronic pain.
Haché, Chantal; Villeneuve, Jean-Pierre
Chronic hepatitis B is a common disease and approximately 20% of infected patients with compensated cirrhosis will decompensate over 5 years. If untreated, the survival of decompensated cirrhosis is poor (15% at 5 years). The extent of hepatitis B virus (HBV) replication, as assessed by serum HBV-DNA level, is a strong predictor of the risk of disease progression and hepatocellular carcinoma. This provides a rationale for antiviral therapy to arrest progression of liver disease. Lamivudine is a pyrimidine analogue that inhibits HBV-DNA reverse transcriptase. It decreases HBV replication, normalises alanine aminotransferase levels and reduces hepatic inflammation and fibrosis in patients with chronic hepatitis B. This article will focus on the use of lamivudine in patients with HBV-cirrhosis. In patients with compensated HBV-cirrhosis, a randomised, placebo-controlled trial has shown that lamivudine significantly reduced the rate of disease progression and hepatocellular carcinoma development over a 3-year period. In patients with decompensated cirrhosis, treatment with lamivudine can produce spectacular improvements of liver function, but the improvement is slow and a clinical benefit is usually not observed until after at least 3-6 months of treatment. A major drawback of lamivudine treatment is the development of resistance, observed in 15-20% of patients after 1 year and up to 70% after 5 years of continued treatment. Thus, patients with HBV-cirrhosis treated with lamivudine should have regular monitoring of serum HBV-DNA levels and prompt institution of additional antiviral therapy if viral breakthrough is observed. Adefovir, tenofovir and entecavir have demonstrated efficacy in patients with lamivudine resistance. In patients with decompensated cirrhosis, in whom the development of resistance can be fatal, combination therapy (such as lamivudine plus adefovir) may prove more effective than monotherapy and this issue needs further study.
Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato
The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics
Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato
The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics
Elhiblu, M. A.; Dua, K.; Mohindroo, J.; Mahajan, S. K.; Sood, N. K.; Dhaliwal, P. S.
Aim: The aim of this study was to determine the relevant tools in the diagnosis of liver cirrhosis in dogs. Material and Methods: A total of 140 dogs presented at Veterinary Teaching Hospital, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, showing clinical signs of hepatic insufficiency were subjected to clinico-hemato biochemical, urological, ultrasonographic (USG), and USG guided fine-needle biopsy examinations by standard methods. On the basis of these results, 6 dogs out of 140 dogs were found to be suffering from liver cirrhosis. Six clinically healthy dogs constituted the control group. Results: The dogs suffering from liver cirrhosis manifested inappetence, halitosis, abdominal distension, weight loss, melena, icterus, anemia, and neutrophilic leukocytosis with the left shift. Levels of hemoglobin, lymphocytes, packed cell volume, mean corpuscular volume, mean corpuscular Hb (MCH), and platelet count were significantly lower in liver cirrhosis group than control group while total leukocyte count, neutrophils, and MCH concentration were significantly higher. Glucose, total protein, albumin, A/G ratio, and fibrinogen were significantly lower, and creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, prothrombin time, and APTT were significantly higher than the control values. Ultrasound revealed diffuse increase in echogenicity with rounded and irregular liver margins. Cytological examination of the ascitic fluid and fine-needle aspiration biopsy of liver was not fruitful in the diagnosis of liver cirrhosis. Conclusions: Liver cirrhosis causes clinical and hemo-biochemical alterations, which require special consideration when treating diseased animals. USG, diffuse increase in echogenicity of liver, rounding and irregularity of liver margins and microhepatica were the consistent findings. It is suggested that USG along with hemo-biochemical alterations may be used as a diagnostic tool for liver cirrhosis
Becker, Ulrik; Grønbaek, Morten; Johansen, Ditte; Sørensen, Thorkild I A
Although there is a well-known relationship between total alcohol intake and future risk for cirrhosis, other factors such as the type of alcohol consumed are sparsely studied. The aim of this study was to assess the effects of wine compared with other types of alcoholic beverages on risk for alcohol-induced cirrhosis. In 3 prospective studies, 30,630 participants from the Copenhagen area were followed-up for a total observation time of 417,325 person-years. Information on weekly intake of beer, wine, and spirits, and sex, age, body mass index, smoking habits, and education was obtained from questionnaires. The primary outcome measures were first admission or death, with alcohol-induced cirrhosis obtained from death certificates and from the National Hospital Discharge Register. Data were analyzed by means of multiplicative Poisson regression models. We confirmed the increasing risk for cirrhosis with increasing alcohol intake. Individuals who drank more than 5 drinks per day had a relative risk of 14 to 20 for developing cirrhosis compared with non- or light drinkers. However, compared with individuals who drank no wine (relative risk set at 1.0), individuals drinking 16% to 30% wine of their total intake had a relative risk of 0.4 (95% confidence limits, 0.3-0.6) and those drinking 51% or more of wine had a relative risk of 0.3 (95% confidence limits, 0.2-0.5) for developing cirrhosis. In conclusion, the results suggest that a high intake of all 3 types of alcohol conveys an increased risk for cirrhosis, but wine drinkers are at a lower risk than beer and spirits drinkers.
Missoni, Eduard; Bozić, Boris; Missoni, Ivan
The aim of this study was to gather enough data in order to formulate theory- and research-based recommendations to policy makers with the intention of decreasing the number of alcohol-related accidents and victims on Croatian roads. The data on the injured traffic participants and the share of participants under the influence of alcohol were collected from the police reports of the Traffic Police Department, Ministry of the Interior, written at the scene of the respective accidents. This documentation was then processed by descriptive epidemiology and analysed through a four-year period, before and after the passing of the New Road Traffic Safety Act in the Republic of Croatia, on 20 August 2004. In the first six months of 2005, after the passing of the Act, there were 3,275 accidents caused by the motorists under the influence of alcohol (12.5% of all the accidents), with 64 persons killed. Only 5 fatalities (8%) were caused by the drivers with measured blood alcohol concentration of up to 0.5 per thousand. As much as 27 fatalities (42%) were caused by the drivers with measured more than 1.5 per thousand, while half of the fatalities, 32 (50%), were caused by drivers with 0.5-1.5 per thousand. In this period, more than 451,000 violations were recorded, whereas in the same period of the previous year, the number of violations was about 519,000. A reduction of the total number of accidents is the result of the new regulation provision, according to which the incidents without human victims do not have to be reported to the police. The number of traffic accidents caused by drivers under the influence of alcohol had increased by some dozen per cents, namely: 2005 - 6,219 persons, 2006- 6,590 persons, noting that in 2006 one less person was killed (123) compared to 2005. In 2005, drivers with alcohol concentration of 0-0.5 per thousand caused 1,096 accidents, with 14 fatalities, whereas in 2006 there were 1,164 accidents with 9 fatalities. A total of 2,314 accidents
Bekman, Nicole M.; Cummins, Kevin; Brown, Sandra A.
This study examines whether expectancies about the impact of not drinking or reducing alcohol use and perceptions of peer alcohol use partially mediated risk incurred by sensation seeking for adolescent alcohol involvement. High school drinkers (N = 3,153) completed a survey assessing substance use, sensation seeking, perceived peer alcohol use,…
Vainshtein, Jeffrey M.; Kabarriti, Rafi; Mehta, Keyur J.; Roy-Chowdhury, Jayanta; Guha, Chandan
Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local disease control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the treatment
Situs inversus totalis is is a congenital anomaly associated with various visceral abnormalities, but there is no data about the relationship between secondary biliary cirrhosis and that condition. We here present a case of a 58 year-old female with situs inversus totalis who was admitted to our clinic with extrahepatic cholestasis. After excluding all potential causes of biliary cirrhosis, secondary biliary cirrhosis was diagnosed based on the patient's history, imaging techniques, clinical and laboratory findings, besides histolopathological findings. After treatment with tauroursodeoxycholic acid, all biochemical parameters, including total/direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gama glutamyl transferase, returned to normal ranges at the second month of the treatment. We think that this is the first case in literature that may indicate the development of secondary biliary cirrhosis in a patient with situs inversus totalis. In conclusion, situs inversus should be considered as a rare cause of biliary cirrhosis in patients with situs inversus totalis which is presented with extrahepatic cholestasis. PMID:21813017
Liu, Hui; Shao, Ying; Guo, Dongmei; Zheng, Yuanjie; Zhao, Zuowei; Qiu, Tianshuang
Accurate staging of hepatic cirrhosis is important in investigating the cause and slowing down the effects of cirrhosis. Computer-aided diagnosis (CAD) can provide doctors with an alternative second opinion and assist them to make a specific treatment with accurate cirrhosis stage. MRI has many advantages, including high resolution for soft tissue, no radiation, and multiparameters imaging modalities. So in this paper, multisequences MRIs, including T1-weighted, T2-weighted, arterial, portal venous, and equilibrium phase, are applied. However, CAD does not meet the clinical needs of cirrhosis and few researchers are concerned with it at present. Cirrhosis is characterized by the presence of widespread fibrosis and regenerative nodules in the hepatic, leading to different texture patterns of different stages. So, extracting texture feature is the primary task. Compared with typical gray level cooccurrence matrix (GLCM) features, texture classification from random features provides an effective way, and we adopt it and propose CCTCRF for triple classification (normal, early, and middle and advanced stage). CCTCRF does not need strong assumptions except the sparse character of image, contains sufficient texture information, includes concise and effective process, and makes case decision with high accuracy. Experimental results also illustrate the satisfying performance and they are also compared with typical NN with GLCM.
Amarapurkar, Pooja D; Amarapurkar, Deepak N
Patients with decompensated liver cirrhosis have significantly impaired synthetic function. Many proteins involved in the coagulation process are synthesized in the liver. Routinely performed tests of the coagulation are abnormal in patients with decompensated liver cirrhosis. This has led to the widespread belief that decompensated liver cirrhosis is prototype of acquired hemorrhagic coagulopathy. If prothrombin time is prolonged more than 3 seconds over control, invasive procedures like liver biopsy, splenoportogram, percutaneous cholangiography, or surgery were associated with increased risk of bleeding, and coagulopathy should be corrected with infusion of fresh frozen plasma. These practices were without any scientific evidence and were associated with significant hazards of fresh frozen plasma transfusion. Now, it is realized that coagulation is a complex process involving the interaction of procoagulation and anticoagulation factors and the fibrinolytic system. As there is reduction in both anti and procoagulant factors, global tests of coagulation are normal in patients with acute and chronic liver disease indicating that coagulopathy in liver disease is more of a myth than a reality. In the last few years, surgical techniques have substantially improved, and complex procedures like liver transplantation can be done without the use of blood or blood products. Patients with liver cirrhosis may also be at increased risk of thrombosis. In this paper, we will discuss coagulopathy, increased risk of thrombosis, and their management in decompensated liver cirrhosis.
Yeom, Suk Keu; Lee, Chang Hee; Cha, Sang Hoon; Park, Cheol Min
Early diagnosis of liver cirrhosis is important. Ultrasound-guided liver biopsy is the gold standard for diagnosis of liver cirrhosis. However, its invasiveness and sampling bias limit the applicability of the method. Basic imaging for the diagnosis of liver cirrhosis has developed over the last few decades, enabling early detection of morphological changes of the liver by ultrasonography (US), computed tomography, and magnetic resonance imaging (MRI). They are also accurate diagnostic methods for advanced liver cirrhosis, for which early diagnosis is difficult. There are a number of ways to compensate for this difficulty, including texture analysis to more closely identify the homogeneity of hepatic parenchyma, elastography to measure the stiffness and elasticity of the liver, and perfusion studies to determine the blood flow volume, transit time, and velocity. Amongst these methods, elastography using US and MRI was found to be slightly easier, faster, and able to provide an accurate diagnosis. Early diagnosis of liver cirrhosis using MRI or US elastography is therefore a realistic alternative, but further research is still needed. PMID:26301049
Mathurin, Sebastián; Chapelet, Adrián; Spanevello, Valeria; Sayago, Gabriel; Balparda, Cecilia; Virga, Eliana; Beraudo, Nora; Bartolomeo, Mirta
We evaluated the prevalence and the clinical relevance of bacterial and nonbacterial infections in predominantly alcoholic cirrhotic patients, admitted to an intermediate complexity hospital, and we also compared the clinical characteristics, laboratory and evolution of these patients with and without bacterial infection in a prospective study of cohort. A total of 211 consecutive admissions in 132 cirrhotic patients, between April 2004 and July 2007, were included. The mean age was 51.8 (+/-8) years, being 84.8% male. The alcoholic etiology of cirrhosis was present in 95.4%. One hundred and twenty nine episodes of bacterial infections were diagnosed in 99/211 (46.9%) admissions, community-acquired in 79 (61.2%) and hospital-acquired in 50 (38.8%): spontaneous bacterial peritonitis (23.3%); urinary tract infection (21.7%); pneumonia (17.8%); infection of the skin and soft parts (17.1%), sepsis by spontaneous bacteremia (7.7%); other bacterial infections (12.4%). Gram-positive organisms were responsible for 52.2% of total bacterial infections documented cases. There were eight serious cases of tuberculosis, fungal and parasitic infections; the prevalence of tuberculosis was 6% with an annual mortality of 62.5%; 28.1% (9/32) of the coproparasitological examination had Strongyloides stercolaris. The in-hospital mortality was significantly higher in patients with bacterial infection than in non-infected patients (32.4% vs. 13.2%; p=0.02). The independent factors associated with mortality were bacterial infections, the score of Child-Pügh and creatininemia > 1.5 mg/dl. By the multivariate analysis, leukocytosis and hepatic encephalopathy degree III/IV were independent factors associated to bacterial infection. This study confirms that bacterial and nonbacterial infections are a frequent and severe complication in hospitalized cirrhotic patients, with an increase of in-hospital mortality.
Graupera, Isabel; Solà, Elsa; Fabrellas, Núria; Moreira, Rebeca; Solé, Cristina; Huelin, Patricia; de la Prada, Gloria; Pose, Elisa; Ariza, Xavier; Risso, Alessandro; Albertos, Sonia; Morales-Ruiz, Manuel; Jiménez, Wladimiro; Ginès, Pere
MCP-1 (monocyte chemoattractant protein-1) is a proinflammatory cytokine involved in chemotaxis of monocytes. In several diseases, such as acute coronary syndromes and heart failure, elevated MCP-1 levels have been associated with poor outcomes. Little is known about MCP-1 in cirrhosis. AIM: To investigate the relationship between MCP-1 and outcome in decompensated cirrhosis. METHODS: Prospective study of 218 patients discharged from hospital after an admission for complications of cirrhosis. Urine and plasma levels of MCP-1 and other urine proinflammatroy biomarkers: osteopontin(OPN), trefoil-factor3 and liver-fatty-acid-binding protein were measured at admission. Urine non-inflammatory mediators cystatin-C, β2microglobulin and albumin were measured as control biomarkers. The relationship between these biomarkers and the 3-month hospital readmission, complications of cirrhosis, and mortality were assessed. RESULTS: 69 patients(32%) had at least one readmission during the 3-month period of follow-up and 30 patients died(14%). Urine MCP-1 and OPN levels, were associated with 3-month probability of readmission (0.85 (0.27–2.1) and 2003 (705–4586) ug/g creat vs 0.47 (0.2–1.1) and 1188 (512–2958) ug/g creat, in patients with and without readmission, respectively; p<0.05; median (IQR)). Furthermore, urine levels of MCP-1 were significantly associated with mortality (1.01 (1–3.6) vs 0.5 (0.2–1.1) μg/g creat, in dead and alive patients at 3 months; p<0.05). Patients with higher levels of urine MCP-1 (above percentile 75th) had higher probability of development of hepatic encephalopathy, bacterial infections or AKI. Urine MCP-1 was an independent predictive factor of hospital readmission and combined end-point of readmission or dead at 3 months. Plasma levels of MCP-1 did not correlated with outcomes. CONCLUSION: Urine, but not plasma, MCP-1 levels are associated with hospital readmission, development of complications of cirrhosis, and mortality. These
Baldassarre, Maurizio; Giannone, Ferdinando A; Napoli, Lucia; Tovoli, Alessandra; Ricci, Carmen S; Tufoni, Manuel; Caraceni, Paolo
Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules providing different central and peripheral effects that are mediated mostly by the specific receptors CB1 and CB2. The EC system is highly upregulated during chronic liver disease and consistent experimental and clinical findings indicate that it plays a role in the pathogenesis of liver fibrosis and fatty liver disease associated with obesity, alcohol abuse and hepatitis C. Furthermore, a considerable number of studies have shown that EC and their receptors contribute to the pathogenesis of the cardio-circulatory disturbances occurring in advanced cirrhosis, such as portal hypertension, hyperdynamic circulatory syndrome and cirrhotic cardiomyopathy. More recently, the EC system has been implicated in the development of ascites, hepatic encephalopathy and the inflammatory response related to bacterial infection. Rimonabant, a selective CB1 antagonist, was the first drug acting on the EC system approved for the treatment of obesity. Unfortunately, it has been withdrawn from the market because of its neuropsychiatric side effects. Compounds able to target selectively the peripheral CB1 receptors are under evaluation. In addition, molecules stimulating CB2 receptor or modulating the activity of enzymes implicated in EC metabolism are promising areas of pharmacological research. Liver cirrhosis and the related complications represent an important target for the clinical application of these compounds.
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent the major clinical entities of chronic cholestatic liver diseases. Both disorders are characterized by portal inflammation and slowly progress to obliterative fibrosis and eventually liver cirrhosis. Although immune-pathogenic mechanisms have been implicated in the pathogenesis of PBC and PSC, neither disorder is considered to be a classical autoimmune disease, as PSC and PBC patients do not respond to immune-suppressants. Furthermore, the decreased bile flow resulting from the immune-mediated tissue assault and the subsequent accumulation of toxic bile products in PBC and PSC not only perpetuates biliary epithelial damage, but also alters the composition of the intestinal and biliary microbiota and its mutual interactions with the host. Consistent with the close association of PSC and inflammatory bowel disease (IBD), the polyclonal hyper IgM response in PBC and (auto-)antibodies which cross-react to microbial antigens in both diseases, an expansion of individual microbes leads to shifts in the composition of the intestinal or biliary microbiota and a subsequent altered integrity of epithelial layers, promoting microbial translocation. These changes have been implicated in the pathogenesis of both devastating disorders. Thus, we will discuss here these recent findings in the context of novel and alternative therapeutic options. PMID:27834858
Said, Eman; Said, Shehta A; Gameil, Nariman M; Ammar, Elsayed M
Sildenafil citrate is a phosphodiesterase-5 inhibitor, approved for the treatment of erectile dysfunction. It enhances nitric-oxide-induced vasodilatation and it promotes angiogenesis. A relationship between angiogenesis and hepatic fibrosis has long been speculated, where the 2 are believed to progress together. In this study, the ability of sildenafil (10 mg·(kg body mass)(-1), orally, once daily) to prevent and also reverse liver fibrosis/cirrhosis experimentally induced by thioacetamide injection (200 mg·kg(-1), intraperitoneal (i.p.), 3 times·week(-1)) in male Sprague-Dawley rats has been investigated. Sildenafil administration, either to prevent or to reverse liver fibrosis/cirrhosis significantly improved the estimated hepatic functions, reduced hepatic hydroxyproline and, in turn, hepatic collagen content, as well as reducing serum levels of the pro-fibrogenic mediator transforming growth factor β1. In co-ordination with such improvement, fibrosis grades declined and fibrosis retracted. Herein, the observed results provide evidence for the potential therapeutic efficacy of sildenafil as an antifibrotic agent.
Iwata, Takashi; Inoue, Kiyotoshi; Nishiyama, Noritoshi; Nagano, Koshi; Izumi, Nobuhiro; Tsukioka, Takuma; Hanada, Shoji; Suehiro, Shigefumi
We aimed to determine the factors predicting liver cirrhosis-related complications in the early postoperative period after lung cancer surgery in patients with liver cirrhosis. We retrospectively reviewed the medical records of patients who underwent curative surgery for primary lung cancer in our institute from January 1990 to March 2007, finding 37 cases with comorbid liver cirrhosis. These patients were divided into two groups, according to whether liver failure, bleeding, and critical infection had occurred postoperatively. Various clinical parameters were analyzed statistically between the bigeminal groups. Liver cirrhosis-related complications occurred in seven of the 37 patients (18.9%). Transient liver failure occurred in two patients (5.4%) after pulmonary resection. Acute intrathoracic bleeding occurred in four cases (10.8%). Two patients died (5.4%) in both cases due to sepsis. Preoperative total bilirubin (P<0.05), and indocyanine green retention rate at 15 min (P<0.05) were significantly higher in patients with liver failure. Only serum value of total bilirubin was an independent risk factor (P<0.05) by multivariate analysis. In predicting death from infection, only preoperative nutritional status was a significant risk factor (P<0.05). To avoid postoperative cirrhosis-related complications, preoperative preparation to improve their liver function and nutrition status is essential.
Chan, Ko-Ling; Chow, Chun-Bong; Lam, Tai-Hing; Ho, Sai-Yin; Wong, Wilfred Hing-Sang; Wong, Margaret Fung-Yee
Background Underage drinking is a prevalent risk behavior and common public health problem. Research shows that alcohol abuse not only affects the quality of life of drinkers themselves. The problems resulting from underage drinking pose substantial costs to society as well. The proposed study will address underage drinking with the use of an Internet campaign, which is a cost-effective way of tackling the problem. Objective The aims of this study are to test the effectiveness of an online quiz competition in changing adolescents’ alcohol-related attitudes and behavior and to explore the feasibility of using Internet viral marketing to reach a significant number of adolescents. Methods The study will constitute a cluster randomized controlled trial for 20 secondary schools (6720 Grade 7-9 students). Schools will be randomized to intervention or control arm with equal likelihood. Students in intervention schools will be invited to take part in the Internet campaign, whereas those in control schools will receive relevant promotional leaflets. Results Alcohol-related attitude and behavior will be the primary outcome measures. The results of the proposed study will provide evidence on the efficacy of an Internet intervention in modifying adolescents’ attitudes and behavior and guide further investigation into the prevention of and intervention in such risk behaviors as underage drinking. The project was funded July 2015, enrollment started September 2015, and results are expected July 2017. Conclusions With the Internet increasingly being recognized as a practical and cost-effective platform for health information delivery, the proposed Internet-based intervention is expected to be more effective in altering adolescents’ alcohol-related attitudes and behaviors than traditional health promotion. ClinicalTrial ClinicalTrials.gov NCT02450344; https://clinicaltrials.gov/ct2/show/NCT02450344 (Archived by WebCite at http://www.webcitation.org/6heB2zMBD) PMID:27252072
Al-Hamoudi, Waleed K.
Liver cirrhosis is associated with a wide range of cardiovascular abnormalities including hyperdynamic circulation, cirrhotic cardiomyopathy, and pulmonary vascular abnormalities. The pathogenic mechanisms of these cardiovascular changes are multifactorial and include neurohumoral and vascular dysregulations. Accumulating evidence suggests that cirrhosis-related cardiovascular abnormalities play a major role in the pathogenesis of multiple life-threatening complications including hepatorenal syndrome, ascites, spontaneous bacterial peritonitis, gastroesophageal varices, and hepatopulmonary syndrome. Treatment targeting the circulatory dysfunction in these patients may improve the short-term prognosis while awaiting liver transplantation. Careful fluid management in the immediate post-transplant period is extremely important to avoid cardiac-related complications. Liver transplantation results in correction of portal hypertension and reversal of all the pathophysiological mechanisms that lead to the cardiovascular abnormalities, resulting in restoration of a normal circulation. The following is a review of the pathogenesis and clinical implications of the cardiovascular changes in cirrhosis. PMID:20616408
Santos, Lívia Alves Amaral
Management of cirrhosis complications has greatly improved, increasing survival and quality of life of the patients. Despite that, some of these complications are still overlooked and scarcely treated, particularly those that are not related to the liver. This is the case of osteoporosis, the only cirrhosis complication that is not solved after liver transplantation, because bone loss often increases after immunosuppressant therapy. In this review, the definitions of bone conditions in cirrhotic patients are analyzed, focusing on the more common ones and on those that have the largest impact on this population. Risk factors, physiopathology, diagnosis, screening strategies, and treatment of osteoporosis in cirrhotic patients are discussed, presenting the more striking data on this issue. Therapies used for particular conditions, such as primary biliary cirrhosis and liver transplantation, are also presented. PMID:27840821
Czeczot, Hanna; Scibior, Dorota; Skrzycki, Michał; Podsiad, Małgorzata
The aim of our studies was the estimation of activities of antioxidant enzymes in patients with liver cirrhosis. We investigated activities of superoxide dismutases (CuZnSOD, MnSOD), catalase (CAT), selenium dependent GSH peroxidase (Se-GSH-Px), selenium independent GSH peroxidase (non-Se-GSH-Px), GSH-S-transferase (GST), GSH reductase (GSHR) and the level ofreduced gutathione (GSH) in cirrhotic and healthy liver tissues. The activities of CuZnSOD, MnSOD, CAT and GSH-dependent enzymes (except GSHR) were found to be lower in cirrhotic tissue compared to healthy liver. Those changes were associated with decrease of GSH level in cirrhotic tissue compared with control liver tissue. Our results show that antioxidant barrier in liver cirrhosis is impaired. It is associated with decrease of glutathione level and changes of activities of antioxidant enzymes (SOD, CAT, GSHPx, GST, GSHR) in liver cirrhosis compared with healthy liver.
Nakayama, Hisashi; Takayama, Tadatoshi
The global distribution of hepatocellular carcinoma (HCC) varies markedly among regions, and patients in East Asia and Central Africa account for about 80% of all cases. The risk factors are hepatitis B, hepatitis C, alcohol, and etc. The risk of carcinogenesis further increases with progression to hepatic cirrhosis in all liver disorders. Radical treatment of HCC by liver resection without causing liver failure has been established as a safe approach through selection of an appropriate range of resection of the damaged liver. This background indicates that both evaluation of hepatic functional reserve and measures against concomitant diseases such as thrombocytopenia accompanying portal hypertension, prevention of rupture of esophageal varices, reliable control of ascites, and improvement of hypoalbuminemia are important issues in liver resection in patients with hepatic cirrhosis. We review the latest information on perioperative management of liver resection in HCC patients with hepatic cirrhosis. PMID:26380653
Pena, M A; Horga, J F; Zapater, P
Liver cirrhosis is the end stage of many different chronic liver diseases and is becoming an important cause of mortality and morbidity across the world. In theory, the numerous physiopathological changes suffered by these patients warrant relevant pharmacokinetic changes in most drugs. However, the influence of these changes on the efficacy and toxicity responses of patients with cirrhosis have been evaluated by few clinical trials and observational studies. As a consequence, therapeutic decisions in these patients are usually complex and subject to uncertainties. In this article, we review the regulatory guidelines to study responses to drugs according to pharmacokinetic variability and the published information that is useful for guiding the dosage adjustment of frequently used drugs in patients with cirrhosis (antivirals, antibiotics, analgesics, etc.) to obtain the best risk-benefit ratio.
Hypervolemic hyponatremia is common in patients with decompensated cirrhosis, resulting from solute-free water retention caused by the stimulation of V2 receptors of the distal nephron by relatively high circulating levels of arginine vasopressin (AVP, a nonapeptide). A nonosmotic secretion of AVP by the hypothalamo-neurohypophysial system is responsible for high plasma AVP concentrations. This hypersecretion of AVP is triggered by a decrease in effective arterial blood volume and arterial pressure caused by splanchnic/systemic vasodilation. Hyponatremia is an independent predictor of mortality in patients with cirrhosis; however, it is still unknown if hyponatremia by itself plays a role or if it is a simple marker of the severity of liver disease. Pharmacological treatments of hypervolemic hyponatremia using drugs that antagonize the binding of AVP to V2 receptors are under evaluation in patients with cirrhosis.
Brasfield, Hope; Morean, Meghan; Febres, Jeniimarie; Shorey, Ryan C.; Moore, Todd; Zucosky, Heather; Elmquist, JoAnna; Wolford-Clevenger, Caitlin; Labrecque, Lindsay; Plasencia, Maribel; Stuart, Gregory L.
Additional work is needed to determine how and/or why the relationship between alcohol use and increased risk for partner aggression exists. Researchers have begun to examine whether alcohol-related outcome expectancies (i.e., beliefs about the cognitive and behavioral effects of alcohol) are associated with partner aggression irrespective of alcohol use. We examined the relationship between alcohol use, alcohol expectancies, and partner aggression among 360 males arrested for a domestic violence offense and court-mandated to treatment. Results indicate that certain alcohol expectancies do play a role in the relationship between alcohol use and some forms of partner aggression. PMID:25519237
Clarke, Nickeisha; Kim, Su-Young; E. Ray, Anne; R. White, Helene; Jiao, Yang; Mun, Eun-Young
This study examined race and gender differences in use of specific types of protective behavioral strategies (PBS) and the moderating effects of race and gender on the relationship between PBS use and alcohol problems, controlling for alcohol use, among a large sample of Asian, Black, and White college drinkers. There were significant racial and gender differences in the types of PBS used. Moderation analyses indicated that PBS were more protective for women than men against experiencing alcohol-related problems. There were no significant race effects or race-by-gender interaction effects on alcohol problems. Implementing PBS may be beneficial for all college students. PMID:26114577
Brasfield, Hope; Morean, Meghan E; Febres, Jeniimarie; Shorey, Ryan C; Moore, Todd M; Zuckosky Zapor, Heather; Elmquist, JoAnna; Wolford-Clevenger, Caitlin; Labrecque, Lindsay; Plasencia, Maribel; Stuart, Gregory L
Additional work is needed to determine how and/or why the relationship between alcohol use and increased risk of partner aggression (PA) exists. Researchers have begun to examine whether alcohol-related outcome expectancies (i.e., beliefs about the cognitive and behavioral effects of alcohol) are associated with PA irrespective of alcohol use. We examined the relationship between alcohol use, alcohol expectancies, and PA among 360 males arrested for a domestic violence offense and court-mandated to treatment. Results indicate that certain alcohol expectancies do play a role in the relationship between alcohol use and some forms of PA.
Bellis, Mark A; Phillips-Howard, Penelope A; Hughes, Karen; Hughes, Sara; Cook, Penny A; Morleo, Michela; Hannon, Kerin; Smallthwaite, Linda; Jones, Lisa
Background There is a lack of empirical analyses examining how alcohol consumption patterns in children relate to harms. Such intelligence is required to inform parents, children and policy relating to the provision and use of alcohol during childhood. Here, we examine drinking habits and associated harms in 15-16 year olds and explore how this can inform public health advice on child drinking. Methods An opportunistic survey of 15-16 year olds (n = 9,833) in North West England was undertaken to determine alcohol consumption patterns, drink types consumed, drinking locations, methods of access and harms encountered. Cost per unit of alcohol was estimated based on a second survey of 29 retail outlets. Associations between demographics, drinking behaviours, alcohol pricing and negative outcomes (public drinking, forgetting things after drinking, violence when drunk and alcohol-related regretted sex) were examined. Results Proportions of drinkers having experienced violence when drunk (28.8%), alcohol-related regretted sex (12.5%) and forgetting things (45.3%), or reporting drinking in public places (35.8%), increased with drinking frequency, binge frequency and units consumed per week. At similar levels of consumption, experiencing any negative alcohol-related outcome was lower in those whose parents provided alcohol. Drunken violence was disproportionately associated with being male and greater deprivation while regretted sex and forgetting things after drinking were associated with being female. Independent of drinking behaviours, consuming cheaper alcohol was related to experiencing violence when drunk, forgetting things after drinking and drinking in public places. Conclusion There is no safe level of alcohol consumption for 15-16 year olds. However, while abstinence removes risk of harms from personal alcohol consumption, its promotion may also push children into accessing drink outside family environments and contribute to higher risks of harm. Strategies to
Shirasu, Naoto; Kuroki, Masahide
We developed a time- and cost-effective multiplex allele-specific polymerase chain reaction (AS-PCR) method based on the two-step PCR thermal cycles for genotyping single-nucleotide polymorphisms in three alcoholism-related genes: alcohol dehydrogenase 1B, aldehyde dehydrogenase 2 and μ-opioid receptor. Applying MightyAmp(®) DNA polymerase with optimized AS-primers and PCR conditions enabled us to achieve effective and selective amplification of the target alleles from alkaline lysates of a human hair root, and simultaneously to determine the genotypes within less than 1.5 h using minimal lab equipment.
Montano-Loza, Aldo J
The most commonly recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, susceptibility for infections, kidney dysfunction, and hepatocellular carcinoma; however, severe muscle wasting or sarcopenia are the most common and frequently unseen complications which negatively impact survival, quality of life, and response to stressor, such as infections and surgeries. At present, D'Amico stage classification, Child-Pugh, and MELD scores constitute the best tools to predict mortality in patients with cirrhosis; however, one of their main limitations is the lack of assessing the nutritional and functional status. Currently, numerous methods are available to evaluate the nutrition status of the cirrhotic patient; nevertheless, most of these techniques have limitations primarily because lack of objectivity, reproducibility, and prognosis discrimination. In this regard, an objective and reproducible technique, such as muscle mass quantification with cross-sectional imaging studies (computed tomography scan or magnetic resonance imaging) constitute an attractive index of nutritional status in cirrhosis. Sarcopenia is part of the frailty complex present in cirrhotic patients, resulting from cumulative declines across multiple physiologic systems and characterized by impaired functional capacity, decreased reserve, resistance to stressors, and predisposition to poor outcomes. In this review, we discuss the current accepted and new methods to evaluate prognosis in cirrhosis. Also, we analyze the current knowledge regarding incidence and clinical impact of malnutrition and sarcopenia in patients with cirrhosis and their impact after liver transplantation. Finally, we discuss existing and potential novel therapeutic approaches for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in an effort to reduced morbidity related and improved survival in cirrhosis.
Fukui, Hiroshi; Saito, Hidetsugu; Ueno, Yoshiyuki; Uto, Hirofumi; Obara, Katsutoshi; Sakaida, Isao; Shibuya, Akitaka; Seike, Masataka; Nagoshi, Sumiko; Segawa, Makoto; Tsubouchi, Hirohito; Moriwaki, Hisataka; Kato, Akinobu; Hashimoto, Etsuko; Michitaka, Kojiro; Murawaki, Toshikazu; Sugano, Kentaro; Watanabe, Mamoru; Shimosegawa, Tooru
The Japanese Society of Gastroenterology revised the evidence-based clinical practice guidelines for liver cirrhosis in 2015. Eighty-three clinical questions were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases for the period between 1983 and June 2012. Manual searching of the latest important literature was added until August 2015. The guidelines were developed with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This digest version in English introduces selected clinical questions and statements related to the management of liver cirrhosis and its complications. Branched-chain amino acids relieve hypoalbuminemia and hepatic encephalopathy and improve quality of life. Nucleoside analogues and peginterferon plus ribavirin combination therapy improve the prognosis of patients with hepatitis B virus related liver cirrhosis and hepatitis C related compensated liver cirrhosis, respectively, although the latter therapy may be replaced by direct-acting antivirals. For liver cirrhosis caused by primary biliary cirrhosis and active autoimmune hepatitis, urosodeoxycholic acid and steroid are recommended, respectively. The most adequate modalities for the management of variceal bleeding are the endoscopic injection sclerotherapy for esophageal varices and the balloon-occluded retrograde transvenous obliteration following endoscopic obturation with cyanoacrylate for gastric varices. Beta-blockers are useful for primary prophylaxis of esophageal variceal bleeding. The V2 receptor antagonist tolvaptan is a useful add-on therapy in careful diuretic therapy for ascites. Albumin infusion is useful for the prevention of paracentesis-induced circulatory disturbance and renal failure. In addition to disaccharides, the nonabsorbable antibiotic rifaximin is useful for the management of encephalopathy. Anticoagulation therapy is proposed for
Nakamoto, Shingo; Kanda, Tatsuo; Shirasawa, Hiroshi; Yokosuka, Osamu
Patients who are infected with hepatitis C virus (HCV) and also have advanced fibrosis or cirrhosis have been recognized as "difficult-to-treat" patients during an era when peginterferon and ribavirin combination therapy is the standard of care. Recent guidelines have clearly stated that treatment should be prioritized in this population to prevent complications such as decompensation and hepatocellular carcinoma. Recent advances in the treatment of chronic hepatitis C have been achieved through the development of direct-acting antiviral agents (DAAs). Boceprevir and telaprevir are first-generation DAAs that inhibit the HCV NS3/4A protease. Boceprevir or telaprevir, in combination with peginterferon and ribavirin, improved the sustained virological response rates compared with peginterferon and ribavirin alone and were tolerated in patients with HCV genotype 1 infection without cirrhosis or compensated cirrhosis. However, the efficacy is lower especially in prior non-responders with or without cirrhosis. Furthermore, a high incidence of adverse events was observed in patients with advanced liver disease, including cirrhosis, in real-life settings. Current guidelines in the United States and in some European countries no longer recommend these regimens for the treatment of HCV. Next-generation DAAs include second-generation HCV NS3/4A protease inhibitors, HCV NS5A inhibitors and HCV NS5B inhibitors, which have a high efficacy and a lower toxicity. These drugs are used in interferon-free or in interferon-based regimens with or without ribavirin in combination with different classes of DAAs. Interferon-based regimens, such as simeprevir in combination with peginterferon and ribavirin, are well tolerated and are highly effective especially in treatment-naïve patients and in patients who received treatment but who relapsed. The efficacy is less pronounced in null-responders and in patients with cirrhosis. Interferon-free regimens in combination with ribavirin and
Wilkinson, S P; Moodie, H; Stamatakis, J D; Kakkar, V V; Williams, R
An investigation into the possible role of endotoxins in the pathogenesis of renal failure in cirrhosis and obstructive jaundice showed the two to be closely related. None of the patients with cirrhosis who had endotoxaemia had other evidence of Gram-negative infection at the time of the study, and the endotoxaemia was therefore probably due to impaired hepatic clearance of toxins normally absorbed from the gastrointestinal tract. In contrast, bacteriological evidence of Gram-negative infection was found in most of the patients with obstructive jaundice and endotoxaemia. PMID:795499
De Robertis, Riccardo; D’Onofrio, Mirko; Demozzi, Emanuele; Crosara, Stefano; Canestrini, Stefano; Pozzi Mucelli, Roberto
Progressive hepatic fibrosis can lead to cirrhosis, so its early detection is fundamental. Staging fibrosis is also critical for prognosis and management. The gold standard for these aims is liver biopsy, but it has several drawbacks, as it is invasive, expensive, has poor acceptance, is prone to inter observer variability and sampling errors, has poor repeatability, and has a risk of complications and mortality. Therefore, non-invasive imaging tests have been developed. This review mainly focuses on the role of transient elastography, acoustic radiation force impulse imaging, and magnetic resonance-based methods for the noninvasive diagnosis of cirrhosis. PMID:24966594
Prince, M.; Jones, D.
Primary biliary cirrhosis (PBC) is a chronic autoimmune disease characterised by cholestatic liver function tests, antimitochondrial antibodies, and abnormal liver histology. Early descriptions of a rare rapidly progressive disease no longer reflect the more indolent progress often seen today. Many patients have significant long term morbidity through symptoms such as fatigue and itch with a minority progressing to liver failure and need for transplantation. The current data on the diagnosis, clinical progression, and treatment of PBC are reviewed. Keywords: primary biliary cirrhosis; liver transplantation; pruritus PMID:10727561
macrophage inflammatory status is higher in ascites of alcohol-related cirrhotic patients than in HCV-related patients, which could be related with differences in bacterial translocation episodes or regulatory T cell populations. These findings should contribute to identifying potential prognostic and/or therapeutic targets for chronic liver diseases of different etiology. PMID:22866973
Traussnigg, Stefan; Kienbacher, Christian; Halilbasic, Emina; Rechling, Christian; Kazemi-Shirazi, Lili; Hofer, Harald; Munda, Petra; Trauner, Michael
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC. The therapeutic options in NAFLD/NASH include lifestyle modification, pharmacological treatment, bariatric surgery for patients with morbid obesity and treatment of complications of liver cirrhosis and HCC, including liver transplantation. Insulin sensitizers and antioxidative treatment strategies with vitamin E are among the best-established pharmacological approaches, but both drugs have long-term safety issues and there is limited evidence in cirrhotic patients. Treatment of concomitant/underlying metabolic conditions with statins or metformin may also have beneficial effects on portal hypertension, complications of liver cirrhosis and HCC prevention. The bile acid receptor FXR may be a promising novel therapeutic target for the treatment of NAFLD/NASH, fibrosis and portal hypertension, but the prognostic implications of associated changes in low- and high-density lipoprotein cholesterol require further studies. Morbidly obese NASH patients can benefit from bariatric surgery which may reduce liver fibrosis but carries a risk of decompensation in patients with advanced liver cirrhosis. When carefully selected, patients with NASH cirrhosis undergoing liver transplantation have a good outcome. This review summarizes recent progress in the management of patients with liver cirrhosis due to NASH.
Munday, William R.; DiCapua, Daniel; Vortmeyer, Alexander; Gomez, Jose Luis
Guillain–Barré syndrome (GBS) is an immune-mediated disorder characterized by acute polyneuropathy, ascending paralysis and post infectious polyneuritis. Two-thirds of patients present with a history of recent upper respiratory tract or gastrointestinal infection. The clinical history, neurologic examination and laboratory assessment allow for a straightforward diagnosis in the majority of cases. However, primary biliary cirrhosis (PBC) is known to cause clinically detectable muscular weakness. It is therefore critical to differentiate between PBC-associated muscular weakness and GBS-induced paralysis. Here, we report a patient with a longstanding history of PBC who developed progressive weakness and respiratory failure due to GBS, which clinically mimicked PBC myopathy. This is the first reported association between GBS and PBC. PMID:26634144
Montoliu, J; Darnell, A; Grau, J M; Torras, A; Revert, L
Six HBsAg negative patients with cirrhosis of the liver (CL) presented with recurrent bouts of palpable purpura in the legs due to small vessel leucocytoclastic vasculitis. In addition, all patients had renal failure, proteinuria and microhaematuria. Renal biopsy disclosed either diffuse proliferative (3 cases) or focal necrotising glomerulonephritis with crescents (2 cases). One patient had IgM-IgG mixed cryoglobulinaemia (type II). Four patients died of complications of their CL. Hepatocellular carcinoma was found in 1 case. In the patient without renal biopsy renal function improved following steroids and cyclophosphamide. The pathogenesis of this syndrome of cutaneous vasculitis with severe glomerular involvement in CL is unknown but could be immune-complex mediated.
LaBrie, Joseph W; Kenney, Shannon R; Napper, Lucy E; Miller, Kevin
The personality trait of impulsivity is predictive of heavy drinking and consequences among college students. The current study examined how impulsivity-measured via positive urgency, negative urgency, and sensation seeking-and a person's beliefs about the role alcohol plays in the college experience relate to drinking and consequences in a sample of 470 college students (mean age=19 years, 61.3% female, 59.8% White). In support of the hypotheses, sensation seeking independently predicted greater drinking, and both positive urgency and negative urgency predicted greater experience of alcohol-related negative consequences after controlling for consumption level. Moreover, alcohol beliefs moderated the relationship between impulsivity types and alcohol outcomes. Among students high (versus low) in sensation seeking, strong beliefs about alcohol's role in college life were related to significantly greater drinking, and among students high (versus low) in negative urgency, endorsing strong beliefs about alcohol's role in college life were related to greater levels of alcohol-related negative consequences. Overall, findings inform college prevention efforts by highlighting the need to distinguish unique facets of impulsivity and examine how they intersect with students' beliefs about alcohol in college.
Mihic, Ljiljana; Wells, Samantha; Graham, Kathryn; Tremblay, Paul F; Demers, Andrée
Situational drinking motives (i.e., motives specific to the drinking situation) as well as respondent-level drinking motives (i.e., usual drinking motives across drinking situations) were examined in terms of their relations with aggression experienced by university students. Secondary, multi-level analyses were conducted on the Canadian Campus Survey (CCS), a national survey of 40 Canadian universities conducted between March 1 and April 30, 2004 (N=6,282). For their three most recent drinking events, students reported their motive for drinking (i.e., situational motive) and whether they had an argument/fight. Respondent-level drinking motives were computed by averaging motives across drinking events. Drinking to cope at the situational-level increased the likelihood of aggression. Respondent-level enhancement motives also increased the risk of aggression. Aesthetic motives were important at both situational and respondent levels decreasing the risk for alcohol-related aggression. Gender did not moderate these relations. These results suggest that prevention programming might benefit from a focus on altering drinking motives, or their underlying causes, in order to reduce alcohol-related aggression among young adults.
Lovecchio, Catherine P; Wyatt, Todd M; DeJong, William
A randomized control trial was conducted at a midsized private university in the Northeast to evaluate the short-term impact of AlcoholEdu for College 8.0, an online alcohol course for first-year students. In September 2007, 1,620 matriculated first-year students were randomly assigned to either a treatment group or an assessment-only control group. Both groups of students completed a baseline survey and knowledge test. Treatment group students finished the course, took a second knowledge test, and 30 days later completed a postintervention survey. Control group students completed the postintervention survey and knowledge test during the same time period. Compared with the control group, treatment group students reported a significantly lower level of alcohol use, fewer negative drinking consequences, and less positive alcohol-related attitudes. AlcoholEdu 8.0 had a positive impact on the first-year students' alcohol-related attitudes, behaviors, and consequences. Additional investigations of online alcohol education courses are warranted.
Bernardi, Mauro; Ricci, Carmen Serena; Santi, Luca
Hyponatremia is common in cirrhosis. It mostly occurs in an advanced stage of the disease and is associated with complications and increased mortality. Either hypovolemic or, more commonly, hypervolemic hyponatremia can be seen in cirrhosis. Impaired renal sodium handling due to renal hypoperfusion and increased arginine-vasopressin secretion secondary to reduced effective volemia due to peripheral arterial vasodilation represent the main mechanisms leading to dilutional hyponatremia in this setting. Patients with cirrhosis usually develop slowly progressing hyponatremia. In different clinical contexts, it is associated with neurological manifestations due to increased brain water content, where the intensity is often magnified by concomitant hyperammonemia leading to hepatic encephalopathy. Severe hyponatremia requiring hypertonic saline infusion is rare in cirrhosis. The management of asymptomatic or mildly symptomatic hyponatremia mainly rely on the identification and treatment of precipitating factors. However, sustained resolution of hyponatremia is often difficult to achieve. V2 receptor blockade by Vaptans is certainly effective, but their long-term safety, especially when associated to diuretics given to control ascites, has not been established as yet. As in other conditions, a rapid correction of long-standing hyponatremia can lead to irreversible brain damage. The liver transplant setting represents a condition at high risk for the occurrence of such complications. PMID:26237020
Hayashi, Hiromitsu; Beppu, Toru; Shirabe, Ken; Maehara, Yoshihiko; Baba, Hideo
Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis, limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures because of an increased risk of bleeding. Multiple factors, including splenic sequestration, reduced activity of the hematopoietic growth factor thrombopoietin, bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents, and antiviral treatment with interferon-based therapy, can contribute to the development of thrombocytopenia in cirrhotic patients. Of these factors, the major mechanisms for thrombocytopenia in liver cirrhosis are (1) platelet sequestration in the spleen; and (2) decreased production of thrombopoietin in the liver. Several treatment options, including platelet transfusion, interventional partial splenic embolization, and surgical splenectomy, are now available for severe thrombocytopenia in cirrhotic patients. Although thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis, their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials. In this review, we propose a treatment approach to thrombocytopenia according to our novel concept of splenic volume, and we describe the current management of thrombocytopenia due to liver cirrhosis.
Kumar, Naveen; Kedarisetty, Chandan Kumar; Kumar, Sachin; Khillan, Vikas; Sarin, Shiv Kumar
Tuberculosis (TB) has been a human disease for centuries. Its frequency is increased manyfold in patients with liver cirrhosis. The gold standard of TB management is a 6-mo course of isoniazid, rifampicin, pyrazinamide and ethambutol. Although good results are seen with this treatment in general, the management of patients with underlying cirrhosis is a challenge. The underlying depressed immune response results in alterations in many diagnostic tests. The tests used for latent TB have many flaws in this group of patients. Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis. Frequency of hepatotoxicity is increased in patients with liver cirrhosis, frequently leading to severe liver failure. There are no established guidelines for the treatment of TB in relation to the severity of liver disease. There is no consensus on the frequency of liver function tests required or the cut-off used to define hepatotoxicity. No specific treatment exists for prevention or treatment of hepatotoxicity, making monitoring even more important. A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment. PMID:24914337
Qin, Nan; Yang, Fengling; Li, Ang; Prifti, Edi; Chen, Yanfei; Shao, Li; Guo, Jing; Le Chatelier, Emmanuelle; Yao, Jian; Wu, Lingjiao; Zhou, Jiawei; Ni, Shujun; Liu, Lin; Pons, Nicolas; Batto, Jean Michel; Kennedy, Sean P; Leonard, Pierre; Yuan, Chunhui; Ding, Wenchao; Chen, Yuanting; Hu, Xinjun; Zheng, Beiwen; Qian, Guirong; Xu, Wei; Ehrlich, S Dusko; Zheng, Shusen; Li, Lanjuan
Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.
Desai, Archita P; Reau, Nancy
Advanced liver disease is becoming more prevalent in the United States. This increase has been attributed largely to the growing epidemic of nonalcoholic fatty liver disease and an aging population infected with hepatitis C. Complications of cirrhosis are a major cause of hospital admissions and readmissions. It is important to target efforts for preventing rehospitalization toward patients with cirrhosis who are at the highest risk for readmission, such as those who have high Model for End-Stage Liver Disease scores, are at risk for fluid/electrolyte abnormalities or overt hepatic encephalopathy recurrence, and those who have comorbid conditions (e.g. diabetes). The heart failure management paradigm may provide valuable insights for managing patients with cirrhosis, given the extensive research on preventing hospital readmission and improving health care utilization in this subpopulation. As quality measures related to hospital readmissions for cirrhosis and its complications are adopted by the Centers for Medicare & Medicaid Services and private payers in the future, understanding drivers of hospital readmissions and health care utilization in this vulnerable population are key to improving quality measure performance.
Aguirre Valadez, Jonathan Manuel; Rivera-Espinosa, Liliana; Méndez-Guerrero, Osvely; Chávez-Pacheco, Juan Luis; García Juárez, Ignacio; Torre, Aldo
Liver cirrhosis is a worldwide public health problem, and patients with this disease are at high risk of developing complications, bacterial translocation from the intestinal lumen to the mesenteric nodes, and systemic circulation, resulting in the development of severe complications related to high mortality rate. The intestinal barrier is a structure with a physical and biochemical activity to maintain balance between the external environment, including bacteria and their products, and the internal environment. Patients with liver cirrhosis develop a series of alterations in different components of the intestinal barrier directly associated with the severity of liver disease that finally increased intestinal permeability. A “leaky gut” is an effect produced by damaged intestinal barrier; alterations in the function of tight junction proteins are related to bacterial translocation and their products. Instead, increasing serum proinflammatory cytokines and hemodynamics modification, which results in the appearance of complications of liver cirrhosis such as hepatic encephalopathy, variceal hemorrhage, bacterial spontaneous peritonitis, and hepatorenal syndrome. The intestinal microbiota plays a fundamental role in maintaining the proper function of the intestinal barrier; bacterial overgrowth and dysbiosis are two phenomena often present in people with liver cirrhosis favoring bacterial translocation. Increased intestinal permeability has an important role in the genesis of these complications, and treating it could be the base for prevention and partial treatment of these complications. PMID:27920543
Barritt IV, A. Sidney; Weinberger, Morris; Paul, John E.; Fried, Bruce; Trogdon, Justin G.
Background Increasingly, patients with multiple chronic conditions are being managed in patient-centered medical homes (PCMH) that coordinate primary and specialty care. However, little is known about the types of providers treating complex patients with diabetes and compensated cirrhosis. Objective We examined the mix of physician specialties who see patients dually-diagnosed with diabetes and compensated cirrhosis. Design Retrospective cross-sectional study using 2000–2013 MarketScan® Commercial Claims and Encounters and Medicare Supplemental Databases. Patients We identified 22,516 adults (≥ 18 years) dually-diagnosed with diabetes and compensated cirrhosis. Patients with decompensated cirrhosis, HIV/AIDS, or liver transplantation prior to dual diagnosis were excluded. Main Measures Physician mix categories: patients were assigned to one of four physician mix categories: primary care physicians (PCP) with no gastroenterologists (GI) or endocrinologists (ENDO); GI/ENDO with no PCP; PCP and GI/ENDO; and neither PCP nor GI/ENDO. Health care utilization: annual physician visits and health care expenditures were assessed by four physician mix categories. Key Results Throughout the 14 years of study, 92% of patients visited PCPs (54% with GI/ENDO and 39% with no GI/ENDO). The percentage who visited PCPs without GI/ENDO decreased 22% (from 63% to 49%), while patients who also visited GI/ENDO increased 71% (from 25% to 42%). Conclusions This is the first large nationally representative study to document the types of physicians seen by patients dually-diagnosed with diabetes and cirrhosis. A large proportion of these complex patients only visited PCPs, but there was a trend toward greater specialty care. The trend toward co-management by both PCPs and GI/ENDOs suggests that PCMH initiatives will be important for these complex patients. Documenting patterns of primary and specialty care is the first step toward improved care coordination. PMID:27783702
Mahmoodi, Somayeh; Rahmatollahi, Mahdieh; Shahsavari, Fatemeh; Shafaroodi, Hamed; Grayesh-Nejad, Siyavash; Dehpour, Ahmad R
Increased nitric oxide (NO) formation is mechanistically linked to pathophysiology of the extrahepatic complications of cirrhosis. NO is formed by either enzymatic or non-enzymatic pathways. Enzymatic production is catalyzed by NO synthase (NOS) while entero-salivary circulation of nitrate and nitrite is linked to non-enzymatic formation of NO under acidic pH in the stomach. There is no data on salivary excretion of nitrate and nitrite in cirrhosis. This study was aimed to investigate salivary levels of nitrate and nitrite in a rat model of biliary cirrhosis. Cirrhosis was induced by bile duct ligation (BDL). Four weeks after the operation, submandibular ducts of anesthetized BDL and control rats were cannulated with polyethylene microtube for saliva collection. Assessment of pH, nitrite and nitrate levels was performed in our research. We also investigated NOS expression by real time RT-PCR to estimate eNOS, nNOS and iNOS mRNA levels in the submandibular glands. Salivary pH was significantly lower in BDL rats in comparison to control animals. We also observed a statistically significant increase in salivary levels of nitrite as well as nitrate in BDL rats while there was no elevation in the mRNA expression of nNOS, eNOS, and iNOS in submandibular glands of cirrhotic groups. This indicates that an increased salivary level of nitrite/nitrate is less likely to be linked to increased enzymatic production of NO in the salivary epithelium. It appears that nitrate/nitrite can be transported from the blood stream by submandibular glands and excreted into saliva as entero-salivary circulation, and this mechanism may have been exaggerated during cirrhosis.
Xuan, Ziming; Blanchette, Jason G.; Heeren, Timothy C.; Swahn, Monica H.; Naimi, Timothy S.
Introduction Stronger alcohol policies predict decreased alcohol consumption and binge drinking in the United States. We examined the relationship between the strength of states’ alcohol policies and alcoholic cirrhosis mortality rates. Methods We used the Alcohol Policy Scale (APS), a validated assessment of policies of the 50 US states and Washington DC, to quantify the efficacy and implementation of 29 policies. State APS scores (theoretical range, 0–100) for each year from 1999 through 2008 were compared with age-adjusted alcoholic cirrhosis death rates that occurred 3 years later. We used Poisson regression accounting for state-level clustering and adjusting for race/ethnicity, college education, insurance status, household income, religiosity, policing rates, and urbanization. Results Age-adjusted alcoholic cirrhosis mortality rates varied significantly across states; they were highest among males, among residents in states in the West census region, and in states with a high proportion of American Indians/Alaska Natives (AI/ANs). Higher APS scores were associated with lower mortality rates among females (adjusted incidence rate ratio [IRR], 0.91 per 10-point increase in APS score; 95% confidence interval [95% CI], 0.84–0.99) but not among males (adjusted IRR, 0.97; 95% CI, 0.90–1.04). Among non-AI/AN decedents, higher APS scores were also associated with lower alcoholic cirrhosis mortality rates among both sexes combined (adjusted IRR, 0.89; 95% CI, 0.82–0.97). Policies were more strongly associated with lower mortality rates among those living in the Northeast and West census regions than in other regions. Conclusions Stronger alcohol policy environments are associated with lower alcoholic cirrhosis mortality rates. Future studies should identify underlying reasons for racial/ethnic and regional differences in this relationship. PMID:26469950
Slade, Tim; Chapman, Cath; Swift, Wendy; Keyes, Katherine; Tonks, Zoe; Teesson, Maree
Objective Historically, alcohol use and related harms are more prevalent in men than in women. However, emerging evidence suggests the epidemiology of alcohol use is changing in younger cohorts. The current study aimed to systematically summarise published literature on birth cohort changes in male-to-female ratios in indicators of alcohol use and related harms. Methods We identified 68 studies that met inclusion criteria. We calculated male-to-female ratios for 3 broad categories of alcohol use and harms (any alcohol use, problematic alcohol use and alcohol-related harms) stratified by 5-year birth cohorts ranging from 1891 to 2001, generating 1568 sex ratios. Random-effects meta-analyses produced pooled sex ratios within these 3 categories separately for each birth cohort. Findings There was a linear decrease over time in the sex ratio for all 3 categories of alcohol use and related harms. Among those born in the early 1900s, males were 2.2 (95% CI 1.9 to 2.5) times more likely than females to consume alcohol, 3.0 (95% CI 1.5 to 6.0) times more likely to drink alcohol in ways suggestive of problematic use and 3.6 (95% CI 0.4 to 30.3) times more likely to experience alcohol-related harms. Among cohorts born in the late 1900s, males were 1.1 (95% CI 1.1 to 1.2) times more likely than females to consume alcohol, 1.2 (95% CI 1.1 to 1.4) times more likely to drink alcohol in ways suggestive of problematic use and 1.3 (95% CI 1.2 to 1.3) times more likely to experience alcohol-related harms. Conclusions Findings confirm the closing male–female gap in indicators of alcohol use and related harms. The closing male–female gap is most evident among young adults, highlighting the importance of prospectively tracking young male and female cohorts as they age into their 30s, 40s and beyond. PMID:27797998
Background Alcohol is a major preventable cause of injury, disability and death in young people. Large numbers of young people with alcohol-related injuries and medical conditions present to hospital emergency departments (EDs). Access to brief, efficacious, accessible and cost effective treatment is an international health priority within this age group. While there is growing evidence for the efficacy of brief motivational interviewing (MI) for reducing alcohol use in young people, there is significant scope to increase its impact, and determine if it is the most efficacious and cost effective type of brief intervention available. The efficacy of personality-targeted interventions (PIs) for alcohol misuse delivered individually to young people is yet to be determined or compared to MI, despite growing evidence for school-based PIs. This study protocol describes a randomized controlled trial comparing the efficacy and cost-effectiveness of telephone-delivered MI, PI and an Assessment Feedback/Information (AF/I) only control for reducing alcohol use and related harm in young people. Methods/design Participants will be 390 young people aged 16 to 25 years presenting to a crisis support service or ED with alcohol-related injuries and illnesses (including severe alcohol intoxication). This single blinded superiority trial randomized young people to (i) 2 sessions of MI; (ii) 2 sessions of a new PI or (iii) a 1 session AF/I only control. Participants are reassessed at 1, 3, 6 and 12 months on the primary outcomes of alcohol use and related problems and secondary outcomes of mental health symptoms, functioning, severity of problematic alcohol use, alcohol injuries, alcohol-related knowledge, coping self-efficacy to resist using alcohol, and cost effectiveness. Discussion This study will identify the most efficacious and cost-effective telephone-delivered brief intervention for reducing alcohol misuse and related problems in young people presenting to crisis support
Desapriya, E; Shimizu, S; Pike, I; Subzwari, S; Scime, G
In June of 2002, a revision to part of the Road Traffic Act drastically increased the penalties for drinking and driving offences in Japan. Most notably, the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.05 mg/ml to 0.03 mg/ml. The rationale for the new lower BAC limit was predicated on the assumption that drinking drivers will comply with the new, lower limit by reducing the amount of alcohol they consume prior to driving, thereby lowering their risk of crash involvement. This, in turn, would lead to fewer alcohol-related crashes. A key limitation of previous lower BAC evaluation research in determining the effectiveness of lower legal BAC limit policies is the assumption of population homogeneity in responding to the laws. The present analysis is unique in this perspective and focuses on the evaluation of the impact of BAC limit reduction on different segments of the population. The chief objective of this research is to quantify the extent to which lowering the legal limit of BAC has reduced male, female and teenager involvement in motor vehicle crashes in Japan since 2002. Most notably, the introduction of reduced BAC limit legislation resulted in a statistically significant decrease in the number of alcohol-impaired drivers on the road in Japan, indicating responsiveness to the legal change among adults and teenagers. In addition, this preliminary assessment appears to indicate that the implementation of 0.03 BAC laws and other associated activities are associated with statistically significant reductions in alcohol-involved motor vehicle crashes. In comparison, the rates of total crashes showed no statistically significant decline nor increase in the period following the introduction of the BAC law, indicating that the lower BAC limit only had an effect on alcohol-related crashes in Japan. The evidence suggests that the lower BAC legal limit and perceived risk of detection are the two most important factors resulting in a
Novo-Veleiro, Ignacio; Cieza-Borrella, Clara; Pastor, Isabel; Chamorro, Antonio-Javier; Laso, Francisco-Javier; González-Sarmiento, Rogelio; Marcos, Miguel
Background Genetic polymorphisms in the RAS gene family are associated with different diseases, which may include alcohol-related disorders. Previous studies showed an association of the allelic variant rs26907 in RASGRF2 gene with higher alcohol intake. Additionally, the rs61764370 polymorphism in the KRAS gene is located in a binding site for the let-7 micro-RNA family, which is potentially involved in alcohol-induced inflammation. Therefore, this study was designed to explore the association between these two polymorphisms and susceptibility to alcoholism or alcoholic liver disease (ALD). Methods We enrolled 301 male alcoholic patients and 156 healthy male volunteers in this study. Polymorphisms were genotyped by using TaqMan® PCR assays for allelic discrimination. Allelic and genotypic frequencies were compared between the two groups. Logistic regression analysis was performed to analyze the inheritance model. Results The A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis (23.2%) compared to alcoholic patients without ALD (14.2%). This difference remained significant in the group of patients with alcohol dependence (28.8% vs. 14.3%) but not in those with alcohol abuse (15.1% vs. 14.4%). Multivariable logistic regression analysis showed that the A allele of this polymorphism (AA or GA genotype) was associated with alcoholic cirrhosis both in the total group of alcoholics (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.32–4.11; P = 0.002) and in the group of patients with alcohol dependence (OR: 3.1, 95% CI: 1.50–6.20; P = 0.001). Allelic distributions of the KRAS polymorphism (rs61764370) did not differ between the groups. Conclusions To our knowledge, this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with ALD in men, particularly in the subgroup of patients with AD. The findings suggest the potential relevance of
Herbal mixtures consisting of puerarin and either polyenylphosphatidylcholine or curcumin provide comprehensive protection against alcohol-related disorders in P rats receiving free choice water and 15% ethanol in pure water.
Singh, Ashok K; Jiang, Yin; Benlhabib, Elhabib; Gupta, Shveta
SPCh or CU may provide alternative therapy for alcohol-related disorders.
Blais, Étienne; Bellavance, François; Marcil, Alexandra; Carnis, Laurent
Except for Quebec, all Canadian provinces have introduced administrative laws to lower the permitted blood alcohol concentration (BAC) to .05% or .04% for driving-or having the care of-a motor vehicle. Using linear mixed effects models for longitudinal data, this study evaluates the effect of administrative BAC laws on fatal alcohol related crashes and law enforcement patterns in Canada from 1987 to 2010. Results reveal a significant decrease of 3.7% (95% C.I.: 0.9-6.5%) in fatally injured drivers with a BAC level equal or greater than .05% following the introduction of these laws. Reductions were also observed for fatally injured drivers with BAC levels greater that .08% and .15%. The introduction of administrative BAC laws led neither to significant changes in the rate of driving while impaired (DWI) incidents reported by police officers nor in the probability of being charged for DWI under the Criminal Code.
Jayawickreme, Nuwan; Yasinski, Carly; Williams, Monnica; Foa, Edna B.
The current study examined gender-specific associations between trauma cognitions, alcohol cravings and alcohol-related consequences in individuals with dually diagnosed PTSD and alcohol dependence (AD). Participants (N = 167) had entered a treatment study for concurrent PTSD and AD; baseline information was collected from participants about PTSD-related cognitions in three areas: negative cognitions about self, negative cognitions about the world, and self-blame; and two aspects of AD, alcohol cravings and consequences of AD. Gender differences were examined while controlling for PTSD severity. The results indicate that negative cognitions about the self are significantly related to alcohol cravings in men but not women, and that interpersonal consequences of AD are significantly related to self-blame in women but not in men. These findings suggest that for individuals with comorbid PTSD and AD, psychotherapeutic interventions that focus on reducing trauma-related cognitions are likely to reduce alcohol cravings in men and relational problems in women. PMID:21480680
Andreuccetti, Gabriel; Carvalho, Heraclito B.; Ye, Yu; Bond, Jason; Monteiro, Maristela; Borges, Guilherme; Cherpitel, Cheryl J.
Background Previous studies have already substantiated alcohol’s causal role in injuries. Yet the role that alcoholic beverage preferences and the drinking context play in the risk for injury is still under-investigated. In this study a cross-national comparison of the association between alcohol and injury focusing on beverage type preference and the drinking context is reported. Methods Emergency department injured patients were interviewed in eight countries from the Latin American and Caribbean (LAC) region. Data on the type of alcoholic beverage, total alcohol volume, and the place where the injury occurred were obtained from patients who reported any alcohol consumption within 6 hours prior to being injured. Patients who did not drink prior to injury were also asked about their typical drinking pattern and the injury place. Differences within- and between-groups were evaluated regarding patients’ typical drinking and drinking before injury. Results Beer was the most prevalent beverage type usually consumed among injured patients across countries, however, patients who drank before injury had a higher typical consumption of spirits than those not drinking prior to injury. The total alcohol volume typically consumed and drinking in public settings were also found to be positively associated with alcohol-related injury. Conclusions A similar beverage-specific association with alcohol-related injury was found across LAC countries, mainly attributed to beer consumption, and spirits drinkers seem to have a greater chance of becoming involved in injury events. Future prevention strategies should inform the public about harms from drinking associated with the context in which drinking takes place. PMID:24556276
Hildebrand, Janina; Maycock, Bruce; Burns, Sharyn; Zhao, Yun; Allsop, Steve; Howat, Peter; Lobo, Roanna
Introduction Harmful drinking among young people is common in Australia and many other countries. Social norms and their influence on adolescents’ alcohol consumption behaviours have received much research attention in recent years. However, there is limited understanding of how social norms related to alcohol are developed and transmitted across social networks and a specific tool that measures these constructs has yet to be developed. This paper outlines the rationale and protocol for the design and validation of a multidimensional survey instrument which measures the development and transmission pathways of alcohol-related norms among adolescents. A longer term aim is to apply the instrument in a respondent-driven sampling study with a large adolescent cohort. Methods and analysis Social Cognitive Theory (SCT) and relevant literature will guide the design of the online survey instrument. Feedback from a practitioner-based stakeholder committee, academic expert panel reviews, focus groups and interviews with adolescents aged 13–17 years in Perth, Western Australia (WA) will serve to ascertain content and face validity. A test–retest will be conducted using a purposive sample of students (n=400) at secondary schools in Perth. The instrument's psychometric properties will be analysed, including exploratory factor analyses, discriminant validity, internal consistency and test–retest reliability. Ethics and dissemination The results of this research will provide public health researchers and practitioners with a comprehensive standardised instrument to explore the characteristics of individual-level and community-level social influences and norms associated with use of alcohol by adolescents and the routes through which these norms are transmitted. The data collected by the instrument is anticipated to inform the design of youth specific interventions with the potential to reduce alcohol-related harms. The Study findings will be disseminated widely through
Gilpin, Nicholas W
The central amygdala (CeA) is uniquely situated to function as an interface between stress- and addiction-related processes. This brain region has long been attributed an important role in aversive (e.g., fear) conditioning, as well as the negative emotional states that define alcohol dependence and withdrawal. The CeA is the major output region of the amygdala and receives complex inputs from other amygdaloid nuclei as well as regions that integrate sensory information from the external environment (e.g., thalamus, cortex). The CeA is functionally and anatomically divided into lateral and medial subdivisions that themselves are interconnected and populated by inhibitory interneurons and projections neurons. Neuropeptides are highly expressed in the CeA, particularly in the lateral subdivision, and the role of many of these peptides in regulating anxiety- and alcohol-related behaviors has been localized to the CeA. This review focuses on two of these peptides, corticotropin-releasing factor (CRF) and neuropeptide Y (NPY), that exhibit a high degree of neuroanatomical overlap (e.g., in CeA) and largely opposite behavioral profiles (e.g., in regulating anxiety- and alcohol-related behavior). CRF and NPY systems in the CeA appear to be recruited and/or up-regulated during the transition to alcohol dependence. These and other neuropeptides may converge on GABA synapses in CeA to control projection neurons and downstream effector regions, thereby translating negative affective states into anxiety-like behavior and excessive alcohol consumption.
Magueur, E; Hagege, H; Attali, P; Singlas, E; Etienne, J P; Taburet, A M
The pharmacokinetics of metoclopramide were investigated after intravenous and oral administration in eight patients with severe alcoholic cirrhosis and in eight healthy volunteers. As a consequence of a 50% lower clearance (0.16 +/- 0.07 vs 0.34 +/- 0.09 l h-1 kg-1, plasma drug concentrations and the half-life of metoclopramide were greater in patients following both routes of drug administration. Volume of distribution (3.1 +/- 0.8 vs 3.4 +/- 1.2 l kg-1) and absolute bioavailability (79 +/- 19 vs 84 +/- 15%) were similar in the two groups. The adverse effects of metoclopramide observed in patients with marked hepatic impairment are likely to result from increased accumulation of the drug as a result of impaired clearance. Consequently a reduction in dose of 50% is recommended in patients with severe liver cirrhosis. PMID:2049236
Reis, Renata Karina; da Silva, Patrícia Costa dos Santos; Silva, Ana Elisa Bauer de Camargo; Atila, Elisabeth
The aim of this study was to describe the process of developing a nursing assessment tool for hospitalized adult patients with liver cirrhosis. A descriptive study was carried out in three stages. First, we conducted a literature review to develop a data collection tool on the basis of the Conceptual Model of Wanda Horta. Second, the data collection tool was assessed through an expert panel. Third, we conducted the pilot testing in hospitalized patients. Most of the comments offered by the panel members were accepted to improve the tool. The final version was in the form of a questionnaire with open-closed questions. The panel members concluded that the tool was useful for accurate nursing diagnosis. Horta's Conceptual Model assisted with the development of this data collection tool to help nurses identify accurate nursing diagnosis in hospitalized patients with liver cirrhosis. We hope that the tool can be used by all nurses in clinical practice. PMID:26425862
Corrigan, Margaret; Hirschfield, Gideon M
Primary biliary cirrhosis is a classical autoimmune liver disease and is present in around 1 in 1,000 women over the age of 40. It has a number of diagnostic characteristics consistent with autoimmune liver injury, in particular, the high specificity of circulating anti-mitochondrial antibodies. Histologically, the disease is reflected as a granulomatous lymphocytic cholangitis that consequently leads to small bile duct loss and cholestasis. Progressive disease is characterised by the development of a biliary cirrhosis, with end-stage features of liver disease ultimately impacting patient outcomes. Studies support a combination of environmental and genetic risk factors that coalesce to lead to loss of immunological tolerance and persistent biliary inflammation. Significant advances have occurred recently in understanding the genetic risk factors for disease, as well as utilising human and murine studies to characterise the nature of the biliary injury and cholestatic response.
Sourianarayanane, Achuthan; Thandassery, Ragesh B
The development of decompensation in patients with cirrhosis is associated with increased mortality. Renal function gradually deteriorates with significant hemodynamic changes associated with decompensated liver disease, but may also rapidly decrease in response to precipitating events. Newer definitions of renal dysfunction may result in early diagnosis, this along with the use of sensitive markers helps in accurate determination of renal function in cirrhosis. Although renal dysfunction progresses slowly in cirrhotic patients, it is associated with increased mortality. Prompt intervention with appropriate management reduces the risk of renal dysfunction, as well as improving survival and quality of life. Appropriate management may include the removal of precipitating causes and use of pharmacological agents supporting circulatory dysfunction. Outcomes following treatment of this condition remain a major concern, especially in patients who develop hepatorenal syndrome. Transplantation of the liver or kidney and liver may be the only option when other modalities of treatment fail. Early transplantation may benefit these patients.
Rodés, J.; Bosch, J.; Arroyo, V.
Four separate types of renal failure in cirrhosis are described: functional renal failure; diuretic induced uraemia; acute tubular necrosis; chronic intrinsic renal disease. Functional renal failure may arise spontaneously or be precipitated by such factors as haemorrhage, surgery, or infection. It carries a poor prognosis but preliminary results of treating this condition with plasma volume expansion in combination with high doses of furosemide are encouraging. PMID:1234328
Liver cirrhosis is associated with complex metabolic disorders, and regularly leads to a catabolic state. Catabolism, malassimilation, but also loss of protein and, frequently, malnutrition, are the main reasons underlying reduced the nutritional status frequently encountered in these patients. This promotes such complications as ascites, diabetes mellitus, encephalopathy, infections and the hepatorenal syndrome. Dietary therapy individually tailored to the course of the disease provides the often increased energy requirement, while also serving to prevent and treat complications.
Moctezuma-Velázquez, Carlos; García-Juárez, Ignacio; Soto-Solís, Rodrigo; Hernández-Cortés, Juan; Torre, Aldo
Prevalence of chronic liver diseases, including liver cirrhosis, is increasing worldwide. The nutritional state assessment in these patients is complicated, and besides anthropometry is based on several other tools in order to be more accurate. Specific dietary recommendations are needed in patients with chronic liver diseases in order to help prevent and treat liver decompensation because malnutrition is an independent predictor of mortality. This review focuses on essential aspects in the nutritional assessment of cirrhotic patients and some general recommendations for their treatment.
Qin, Huimin; Li, Hongtao; Xing, Mingyou; Wu, Chunming; Li, Guojun; Song, Jianxin
The therapeutic effectiveness of nutritional support in the treatment of severe chronic hepatitis and posthepatitic cirrhosis was evaluated. 143 patients with severe chronic hepatitis and 83 with posthepatitic cirrhosis were evaluated with SGA for assessing the nutritional status before the treatment. Patients with severe chronic hepatitis were divided into three groups: group A subject to enteral nutrition (EN) and parenteral nutrition (PN), group B subject to comprehensive treatment (CT)+PN; group C subject to CT+EN. The patients with posthepatitic cirrhosis were divided into two groups: group D receiving CT and group E receiving CT+PN+EN. The function of liver and kidney and nutritional status were monitored to assess the therapy in 6 weeks. The results showed before treatment, over 90 % patients had moderate to severe malnutrition. After nutritional support, the liver function (ALT, T-bil) and nutritional status (TP, TC) in group A was improved significantly as compared with that in groups B and C (P<0.05). Compared with group D, the values of TP and Alb were increased significantly in group E (P<0.05), but the levels of ALT, AST and T-bil had no obvious change. It was suggested that most patients with severe chronic hepatitis or posthepatitic cirrhosis had malnutrition to varying degrees. The nutritional support treatment could obviously improve the nutritional status of these patients, and was helpful to ameliorate the liver function of the patients with severe chronic hepatitis. Among the methods of nutritional support treatment, PN combined with EN had the best effectiveness.
Jiang, Mingming; Zeng, Qingfang; Dai, Suiping; Liang, Huixia; Dai, Fengying; Xie, Xueling; Lu, Kunlin; Gao, Chunfang
Gene expression data of hepatocellular carcinoma (HCC) was compared with that of cirrhosis (C) to identify critical genes in HCC. A total of five gene expression data sets were downloaded from Gene Expression Omnibus. HCC and healthy samples were combined as dataset HCC, whereas cirrhosis samples were included in dataset C. A network was constructed for dataset HCC with the package R for performing Weighted Gene Co‑expression Network Analysis. Modules were identified by cluster analysis with the packages flashClust and dynamicTreeCut. Hub genes were screened out by calculating connectivity. Functional annotations were assigned to the hub genes using the Database for Annotation, Visualization and Integration Discovery, and functional annotation networks were visualized with Cytoscape. Following the exclusion of outlier samples, 394 HCC samples and 47 healthy samples were included in dataset HCC and 233 cirrhosis samples were included in dataset C. A total of 6 modules were identified in the weighted gene co‑expression network of dataset HCC (blue, brown, turquoise, green, red and yellow). Modules blue, brown and turquoise had high preservation whereas module yellow exhibited the lowest preservation. These modules were associated with transcription, mitosis, cation transportation, cation homeostasis, secretion and regulation of cyclase activity. Various hub genes of module yellow were cytokines, including chemokine (C‑C motif) ligand 22 and interleukin‑19, which may be important in the development of HCC. Gene expression profiles of HCC were compared with those of cirrhosis and numerous critical genes were identified, which may contribute to the progression of HCC. Further studies on these genes may improve the understanding of HCC pathogenesis.
The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression. PMID:27987536
Goyal, N; Jain, N; Rachapalli, V; Cochlin, D L; Robinson, M
Ultrasound (US) is essential in both assessment of the potentially cirrhotic liver and surveillance of selected patients with chronic hepatitis as liver biopsy can be misleading or inaccurate in up to 25% of cases. Various techniques are already in routine use, such as grey-scale imaging, Doppler US, and contrast-enhanced US (CEUS), while newer techniques such as elastography and hepatic vein transit time (HVTT) have the potential to exclude patients without significant fibrosis or cirrhosis; however, they are operator dependent and require specific software. Grey-scale imaging may demonstrate changes, such as volume redistribution, capsule nodularity, parenchymal nodularity, and echotexture changes. The Doppler findings in the hepatic and portal veins, hepatic artery, and varices allow assessment of liver cirrhosis. However, the operator needs to be aware of limitations of these techniques. Low mechanical index CEUS plays an important role in the assessment of complications of cirrhosis, such as hepatocellular carcinoma and portal vein thrombus. Optimized US technique is crucial for accurate diagnosis of the cirrhotic liver and its complications.
Gehling, Ursula M; Willems, Marc; Schlagner, Kathleen; Benndorf, Ralf A; Dandri, Maura; Petersen, Jörg; Sterneck, Martina; Pollok, Joerg-Matthias; Hossfeld, Dieter K; Rogiers, Xavier
AIM: To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS: Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry. Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1 (SDF-1) were measured using an enzyme linked immunosorbent assay. RESULTS: Progenitor cells with a CD133+/CD45+/CD14+ phenotype were observed in 61% of the patients. Between 1% and 26% of the peripheral blood mononuclear cells (MNCs) displayed this phenotype. Furthermore, a distinct population of c-kit+ progenitor cells (between 1% and 38 % of the MNCs) could be detected in 91% of the patients. Additionally, 18% of the patients showed a population of progenitor cells (between 1% and 68% of the MNCs) that was characterized by expression of breast cancer resistance protein-1. Further phenotypic analysis disclosed that the circulating precursors expressed CXC chemokine receptor 4, the receptor for SDF-1. In line with this finding, elevated plasma levels of SDF-1 were present in all patients and were found to correlate with the number of mobilized CD133+ progenitor cells. CONCLUSION: These data indicate that in humans, liver cirrhosis leads to recruitment of various populations of hematopoietic progenitor cells that display markers of intrahepatic progenitor cells. PMID:20066741
Fernandes, Sabrina Alves; de Mattos, Angelo Alves; Tovo, Cristiane Valle; Marroni, Claudio Augusto
Protein-calorie malnutrition (PCM) is a common condition in cirrhotic patients, leading to a worse prognosis, complications, poor quality of life and lower survival rates. Among ways of assessing nutritional status, there are anthropometric methods such as the evaluation of the triceps skinfold, the arm circumference, the arm muscle circumference and the body mass index, and non-anthropometric methods such as the subjective global assessment, the handgrip strength of non-dominant hand, and the bioelectrical impedance analysis (BIA). PCM is frequently under-diagnosed in clinical settings in patients with cirrhosis due to the limitations of nutritional evaluation methods in this population. BIA is a useful method, but cannot be indicated in patients with abnormal body composition. In these situations, the phase angle (PA) has been used, and can become an important tool in assessing nutritional status in any situation. The PA is superior to anthropometric methods and might be considered as a nutritional indicator in cirrhosis. The early characterization of the nutritional status in patients with cirrhosis means an early nutritional intervention, with a positive impact on patients’ overall prognosis. Among the usually accepted methods for nutritional diagnosis, the PA provides information in a quick and objective manner. PMID:27803765
Goubraim, Rabia; Kabbaj, Nawal; Salihoun, Mouna; Chaoui, Zakia; Nya, M'Hamed; Amrani, Naima
Background/Aim. Metabolic Bone disorders are well-recognized extrahepatic complications of cirrhosis. The aim was to report their prevalence and the associated factors to their development in patients with viral cirrhosis. Patients and Methods. All consecutive patients with viral cirrhosis were prospectively enrolled. Parathyroid hormone, 25-hydroxyvitamin D, liver function, and phosphocalcic tests were measured in all patients. Bone mineral density was measured at the lumbar spine and total hip by dual-energy X-ray absorptiometry. Data were analyzed using SPSS software. Results. Forty-six cirrhotic patients were included with hepatitis C (87%) and hepatitis B (13%). The Child-Pugh score was grade A in 87% of cases and grade B in 13%. Thirty-seven patients had decreased bone mineral density with osteopenia in 24 patients and osteoporosis in 13 patients. Decreased 25-hydroxyvitamin D was found in 95.6% of cases. Bone disorders were significantly more frequent in old patients with low body mass index, long duration of liver disease, and low 25-hydroxyvitamin D level. None of these factors was an independent factor associated with bone disorders. Conclusion. Our study revealed a high prevalence of metabolic bone disorders among viral cirrhotic patients. Consequently, bone mineral density assessment should be performed systematically in all cirrhotic patients. PMID:27398385
No alternative therapeutic option exists if liver cirrhosis patients have insufficient response to conventional diuretics and/or experience conventional diuretic-related adverse events. In 2013, tolvaptan (7.5 mg/day), an arginine vasopressin V2 receptor antagonist, was approved in Japan for the treatment of liver cirrhosis with oedema. Short-term use of tolvaptan produced decreases in body weight, reduction in ascites volume and increases in urine volume when compared to placebo, despite the use of conventional diuretics. Additionally, approximately 60% of patients with oedema-related symptoms improved. Low-dose tolvaptan, 3.75 mg, was also efficacious. Even in patients with low serum albumin (<2.5 g/dL), decrease in body weight was greater with tolvaptan than with placebo. For future research, the efficacy and safety of lower tolvaptan doses for the treatment of liver cirrhosis patients with oedema should be confirmed in Japan. The results of this research could be used as an indicator or a guideline for physicians around the world.
The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression.
Mahamoud, Hawa D.; Muse, Sabah Mohammed; Roberts, Lewis R.; Torbenson, Michael S.; Fader, Tim
Background Khat chewing is common especially among men in East Africa and Yemen. It is generally viewed by the populace as a benign social custom. Several studies of ethnic Somali immigrants to Western countries suggest an association between khat chewing and hepatotoxicity, but the risk of hepatotoxicity related to khat chewing within African settings is not documented. Aim To identify and describe liver disease without evidence of alcohol exposure or infectious etiology in khat chewers. Settings A university-affiliated teaching hospital in Somaliland. Methods Cases of cirrhosis of unknown cause were identified from the clinical practice of Al Hayatt Hospital in Borama, Somaliland, during 14 months beginning December 2012. Results Eight Somali men aged 27–70 years living in Somaliland were identified with cirrhosis of otherwise unknown cause. All chewed khat habitually for many years (15–128 bundles per day times years of use). A liver biopsy of one man was consistent with khat hepatotoxicity. Four of the eight men died during the study period. Conclusion Khat chewing may be associated with health consequences including severe hepatotoxicity with cirrhosis. PMID:27543281
Chen, Ching-Chang; Huang, Yin-Cheng; Yeh, Chun-Nan
Liver cirrhosis, a devastating liver fibrosis caused by hepatitis/inflammation or tumors, is a major comorbid factor in known surgery fields, such as cardiovascular and abdominal surgeries. It is important to review possible comorbid results in neurosurgical procedures in cirrhotic patients. In the reviewed literature, Child-Pugh and model for end-stage liver disease scores are commonly used in the assessment of surgical risks for cirrhotic patients undergoing abdominal, cardiovascular or neurosurgical procedures. The major categories of neurosurgery are traumatic brain injury (TBI), spontaneous intracranial hemorrhage (SICH), brain tumors, and spinal instrumentation procedures. TBI was reported with surgical mortality as high as 34.5% and a complication rate of 87.2%. For SICH, mortality ranged from 22.7% to 47.0%, while complications were reported to be 43.2%. Less is discussed in brain tumor patients; still the postoperative hemorrhage rate approached 26.7%. In spinal fusion instrumentation procedures, the complication rate was as high as 41.0%. Preoperative assessment and correction could possibly decrease complications such as hemorrhage, wound infection and other cirrhosis-related complications (renal, pulmonary, ascites and encephalopathy). In this study, we reviewed the neurosurgical-related literature with regard to liver cirrhosis as a prognostic factor influencing neurosurgical outcomes. PMID:26413225
Safaei, Akram; Rezaei Tavirani, Mostafa; Arefi Oskouei, Afsaneh; Zamanian Azodi, Mona; Mohebbi, Seyed Reza; Nikzamir, Abdol Rahim
Aim: Evaluation of biological characteristics of 13 identified proteins of patients with cirrhotic liver disease is the main aim of this research. Background: In clinical usage, liver biopsy remains the gold standard for diagnosis of hepatic fibrosis. Evaluation and confirmation of liver fibrosis stages and severity of chronic diseases require a precise and noninvasive biomarkers. Since the early detection of cirrhosis is a clinical problem, achieving a sensitive, specific and predictive novel method based on biomarkers is an important task. Methods: Essential analysis, such as gene ontology (GO) enrichment and protein-protein interactions (PPI) was undergone EXPASy, STRING Database and DAVID Bioinformatics Resources query. Results: Based on GO analysis, most of proteins are located in the endoplasmic reticulum lumen, intracellular organelle lumen, membrane-enclosed lumen, and extracellular region. The relevant molecular functions are actin binding, metal ion binding, cation binding and ion binding. Cell adhesion, biological adhesion, cellular amino acid derivative, metabolic process and homeostatic process are the related processes. Protein-protein interaction network analysis introduced five proteins (fibroblast growth factor receptor 4, tropomyosin 4, tropomyosin 2 (beta), lectin, Lectin galactoside-binding soluble 3 binding protein and apolipoprotein A-I) as hub and bottleneck proteins. Conclusion: Our result indicates that regulation of lipid metabolism and cell survival are important biological processes involved in cirrhosis disease. More investigation of above mentioned proteins will provide a better understanding of cirrhosis disease. PMID:27099671
Rector, W.G. Jr.; Ibarra, F.
Previous studies of blood volume (BV) in cirrhosis have either not adjusted BV properly for body size; determined plasma volume from the dilution of labeled albumin 10-20 min postinjection, when some extravascular redistribution has already occurred; and/or not used the correct whole body-peripheral hematocrit ratio (0.82) in calculating whole BV from plasma volume and the peripheral hematocrit. We measured BV with attention to these considerations in 19 patients with cirrhosis and reexamined the determinants of vascular volume and the relationship between vascular volume and sodium retention. BV was calculated as plasma volume (determined from extrapolated plasma activity of intravenously injected (/sup 131/I)+albumin at time 0) divided by (peripheral hematocrit X 0.82). The result was expressed per kilogram dry body weight, determined by subtracting the mass of ascites (measured by isotope dilution; 1 liter = 1 kg) from the actual body weight of nonedematous patients. Measured and expressed in this way, BV correlated strongly with esophageal variceal size (r = 0.87, P less than 0.05), although not with net portal, right atrial, inferior vena caval, or arterial pressure, and was significantly greater in patients with sodium retention as compared to patients without sodium retention. The principal modifier of vascular volume in cirrhosis is vascular capacity, which is probably mainly determined by the extent of the portasystemic collateral circulation. Increased vascular volume in patients with sodium retention as compared to patients without sodium retention supports the overflow theory of ascites formation.
Yamashita, Suguru; Tanaka, Nobutaka; Nomura, Yukihiro; Miyahara, Takuya; Furuya, Takatoshi
Iliopsoas muscle hematoma in a patient with alcoholic liver cirrhosis is rarely seen, however it has a high mortality. Thus we should cautiously make a diagnosis and treatment. This is the case of a 60-year-old male. He had a 15-year history of alcoholic liver disease and emphysema. He presented with low back pain after a fall that had happened 2 months before. Due to persistent back pain, he went to see a local physician who, after detailed examination, suspected rupture of bilateral common iliac artery aneurysms and transferred the patient to our hospital. The same presumptive diagnosis was made, and on this basis, an aortic bifemoral Y-graft was implanted. He developed aspiration pneumonia and hepatic and renal dysfunction postoperatively, which led to multiple organ failure and subsequent in-hospital death on postoperative day 62. This was believed to be a case of iliopsoas muscle hematoma developed in a patient with liver cirrhosis, and considering it was a case with poor surgical risk, a conservative treatment option such as transcatheter arterial embolization should also have been considered. Although iliopsoas muscle hematoma with alcoholic liver cirrhosis is rare, an appropriate treatment plan should be determined on a case-by-case basis despite its poor prognosis.
Jung, Young Kul; Yim, Hyung Joon
In the past, liver cirrhosis was considered an irreversible phenomenon. However, many experimental data have provided evidence of the reversibility of liver fibrosis. Moreover, multiple clinical studies have also shown regression of fibrosis and reversal of cirrhosis on repeated biopsy samples. As various etiologies are associated with liver fibrosis via integrated signaling pathways, a comprehensive understanding of the pathobiology of hepatic fibrogenesis is critical for improving clinical outcomes. Hepatic stellate cells play a central role in hepatic fibrogenesis upon their activation from a quiescent state. Collagen and other extracellular material components from activated hepatic stellate cells are deposited on, and damage, the liver parenchyma and vascular structures. Hence, inactivation of hepatic stellate cells can lead to enhancement of fibrolytic activity and could be a potential target of antifibrotic therapy. In this regard, continued efforts have been made to develop better treatments for underlying liver diseases and antifibrotic agents in multiple clinical and therapeutic trials; the best results may be expected with the integration of such evidence. In this article, we present the underlying mechanisms of fibrosis, current experimental and clinical evidence of the reversibility of liver fibrosis/cirrhosis, and new agents with therapeutic potential for liver fibrosis. PMID:28171717
115 Cirrhosis is the final common pathway on the spec- trum of many types of chronic liver injury.1 In the United States, the two most common causes... cirrhosis are bridg- ing fibrous septa, the formation of regenerative parenchymal nodules, and disruption to the entire hepatic architecture.3 This...coagulopathy, and various meta- bolic abnormalities.1 Little has been reported on the contribution of cirrhosis as a premorbid condition on outcomes
Prystupa, Andrzej; Dąbrowska, Anna; Sak, Jarosław Jerzy; Tarach, Jerzy; Toruń-Jurkowska, Anna; Lachowska-Kotowska, Patrycja; Dzida, Grzegorz
The aim of the present study was to evaluate the concentrations of fetuin-A, osteoprotegerin (OPG) and α-Klotho protein in patients with alcoholic cirrhosis at different stages of the disease, and to demonstrate that fetuin-A, osteoprotegin and α-Klotho may be used as markers of the severity of cirrhosis. A total of 54 patients with alcoholic liver cirrhosis treated in various hospitals in the Lublin region of Poland were randomly enrolled. The control group consisted of 18 healthy individuals without liver disease, who did not drink alcohol. Serum levels of fetuin-A, OPG and α-Klotho were measured by ELISA kits. Levels of fetuin-A were significantly reduced in patients with alcoholic liver cirrhosis compared with the control group. OPG levels were higher in patients with alcoholic liver cirrhosis than in the controls, whereas the levels of α-Klotho were comparable in the cirrhosis and control groups. No statistically significant differences in the concentrations of fetuin-A, OPG and α-Klotho protein were demonstrated according to type of liver cirrhosis. The findings of the present study revealed a significant negative correlation between the level of α-Klotho protein and C-reactive protein in the patients with alcoholic liver cirrhosis. Concentrations of fetuin-A were lower, whereas those of OPG were higher, in the alcoholic liver cirrhosis group compared with the control group. Fetuin-A, OPG and α-Klotho may not be good indicators of liver cirrhosis severity. In conclusion, fetuin-A and OPG may be used in the diagnosis of liver cirrhosis. PMID:27882180
Whitcomb, David C.; LaRusch, Jessica; Krasinskas, Alyssa M.; Klei, Lambertus; Smith, Jill P.; Brand, Randall E.; Neoptolemos, John P.; Lerch, Markus M.; Tector, Matt; Sandhu, Bimaljit S.; Guda, Nalini M.; Orlichenko, Lidiya; Alkaade, Samer; Amann, Stephen T.; Anderson, Michelle A.; Baillie, John; Banks, Peter A.; Conwell, Darwin; Coté, Gregory A.; Cotton, Peter B.; DiSario, James; Farrer, Lindsay A.; Forsmark, Chris E.; Johnstone, Marianne; Gardner, Timothy B.; Gelrud, Andres; Greenhalf, William; Haines, Jonathan L.; Hartman, Douglas J.; Hawes, Robert A.; Lawrence, Christopher; Lewis, Michele; Mayerle, Julia; Mayeux, Richard; Melhem, Nadine M.; Money, Mary E.; Muniraj, Thiruvengadam; Papachristou, Georgios I.; Pericak-Vance, Margaret A.; Romagnuolo, Joseph; Schellenberg, Gerard D.; Sherman, Stuart; Simon, Peter; Singh, Vijay K.; Slivka, Adam; Stolz, Donna; Sutton, Robert; Weiss, Frank Ulrich; Wilcox, C. Mel; Zarnescu, Narcis Octavian; Wisniewski, Stephen R.; O'Connell, Michael R.; Kienholz, Michelle L.; Roeder, Kathryn; Barmada, M. Michael; Yadav, Dhiraj; Devlin, Bernie; Albert, Marilyn S.; Albin, Roger L.; Apostolova, Liana G.; Arnold, Steven E.; Baldwin, Clinton T.; Barber, Robert; Barnes, Lisa L.; Beach, Thomas G.; Beecham, Gary W.; Beekly, Duane; Bennett, David A.; Bigio, Eileen H.; Bird, Thomas D.; Blacker, Deborah; Boxer, Adam; Burke, James R.; Buxbaum, Joseph D.; Cairns, Nigel J.; Cantwell, Laura B.; Cao, Chuanhai; Carney, Regina M.; Carroll, Steven L.; Chui, Helena C.; Clark, David G.; Cribbs, David H.; Crocco, Elizabeth A.; Cruchaga, Carlos; DeCarli, Charles; Demirci, F. Yesim; Dick, Malcolm; Dickson, Dennis W.; Duara, Ranjan; Ertekin-Taner, Nilufer; Faber, Kelley M.; Fallon, Kenneth B.; Farlow, Martin R.; Ferris, Steven; Foroud, Tatiana M.; Frosch, Matthew P.; Galasko, Douglas R.; Ganguli, Mary; Gearing, Marla; Geschwind, Daniel H.; Ghetti, Bernardino; Gilbert, John R.; Gilman, Sid; Glass, Jonathan D.; Goate, Alison M.; Graff-Radford, Neill R.; Green, Robert C.; Growdon, John H.; Hakonarson, Hakon; Hamilton-Nelson, Kara L.; Hamilton, Ronald L.; Harrell, Lindy E.; Head, Elizabeth; Honig, Lawrence S.; Hulette, Christine M.; Hyman, Bradley T.; Jicha, Gregory A.; Jin, Lee-Way; Jun, Gyungah; Kamboh, M. Ilyas; Karydas, Anna; Kaye, Jeffrey A.; Kim, Ronald; Koo, Edward H.; Kowall, Neil W.; Kramer, Joel H.; Kramer, Patricia; Kukull, Walter A.; LaFerla, Frank M.; Lah, James J.; Leverenz, James B.; Levey, Allan I.; Li, Ge; Lin, Chiao-Feng; Lieberman, Andrew P.; Lopez, Oscar L.; Lunetta, Kathryn L.; Lyketsos, Constantine G.; Mack, Wendy J.; Marson, Daniel C.; Martin, Eden R.; Martiniuk, Frank; Mash, Deborah C.; Masliah, Eliezer; McKee, Ann C.; Mesulam, Marsel; Miller, Bruce L.; Miller, Carol A.; Miller, Joshua W.; Montine, Thomas J.; Morris, John C.; Murrell, Jill R.; Naj, Adam C.; Olichney, John M.; Parisi, Joseph E.; Peskind, Elaine; Petersen, Ronald C.; Pierce, Aimee; Poon, Wayne W.; Potter, Huntington; Quinn, Joseph F.; Raj, Ashok; Raskind, Murray; Reiman, Eric M.; Reisberg, Barry; Reitz, Christiane; Ringman, John M.; Roberson, Erik D.; Rosen, Howard J.; Rosenberg, Roger N.; Sano, Mary; Saykin, Andrew J.; Schneider, Julie A.; Schneider, Lon S.; Seeley, William W.; Smith, Amanda G.; Sonnen, Joshua A.; Spina, Salvatore; Stern, Robert A.; Tanzi, Rudolph E.; Trojanowski, John Q.; Troncoso, Juan C.; Tsuang, Debby W.; Valladares, Otto; Van Deerlin, Vivianna M.; Van Eldik, Linda J.; Vardarajan, Badri N.; Vinters, Harry V.; Vonsattel, Jean Paul; Wang, Li-San; Weintraub, Sandra; Welsh-Bohmer, Kathleen A.; Williamson, Jennifer; Woltjer, Randall L.; Wright, Clinton B.; Younkin, Steven G.; Yu, Chang-En; Yu, Lei
Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07. PMID:23143602
Ramamoorthi, Ramya; Jayaraj, Rama; Notaras, Leonard; Thomas, Mahiban
Alcohol - related violence among Australian Aboriginal and Torres Strait Islanders (also called as "Indigenous") is a major public health concern in Northern Territory of Australia. There is dearth of epidemiological data that link three contributing epidemics: alcohol misuse, violence, and trauma in the Northern Territory. In this review, we aimed to concentrate on how these epidemics intersect among the Indigenous people in the Northern Territory. In our descriptive review, we have searched published papers, publicly available government and health department reports web sites reporting relevant data on these three risk factors in the Northern Territory. The high rate of family and domestic violence and assaults in the Australian Territory indicates an increased correlation with high risk alcohol use compared to unintentional injuries. Heavy drinking pattern and harmful use of alcohol among Indigenous people are more likely to be associated with the incidence of violent assaults and physical injuries in the Northern Territory. We are trying to emphasize our understanding of co-occurring risk factors on the alcohol - violence relationship and urging a need for interventional approaches to reduce the public health issues in the Northern Territory.
Lewis, Melissa A.; Neighbors, Clayton; Geisner, Irene Markman; Lee, Christine M.; Kilmer, Jason R.; Atkins, David C.
The present study examined a range of injunctive norms for alcohol use and related consequences from less severe behaviors (e.g., drinking with friends) to more severe behaviors (e.g., drinking enough alcohol to pass out), and their relationship with alcohol consumption and alcohol-related negative consequences among college students. In addition, this research aimed to determine if these relationships between injunctive norms and consequences were moderated by alcohol consumption and level of identification with the typical same-sex college student. A random sample (N = 1,002) of undergraduates (56.9% female) completed a Web–based survey that was comprised of measures of drinking behavior, perceived approval of drinking behaviors that ranged in severity (i.e., injunctive norms), and level of identification with the typical same-sex college student. Results suggest that the association between negative consequences and injunctive drinking norms depend on one's own drinking behavior, identification with other students, and the severity of the alcohol use and related consequences for which injunctive norms are assessed. Findings are discussed in terms of false consensus and false uniqueness effects, and deviance regulation perspectives. Implications for preventative interventions are discussed. PMID:20565144
Smyk, Daniel S; Rigopoulou, Eirini I; Muratori, Luigi; Burroughs, Andrew K; Bogdanos, Dimitrios P
Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the immune-mediated destruction of biliary epithelial cells in small intrahepatic bile ducts. The disease is characterised by circulating anti-mitochondrial antibodies (AMA) as well as disease specific anti-nuclear antibodies (ANA), cholestatic liver biochemistry, and characteristic histology. The disease primarily affects middle-aged females, and its incidence is apparently increasing worldwide. Epidemiological studies have indicated several risk factors for the development of PBC, with family history of PBC, recurrent urinary tract infection, and smoking being the most widely cited. Smoking has been implicated as a risk factor in several autoimmune diseases, including the liver, by complex mechanisms involving the endocrine and immunological systems to name a few. Studies of smoking in liver disease have also shown that smoking may progress the disease towards fibrosis and subsequent cirrhosis. This review will examine the literature surrounding smoking as a risk factor for PBC, as well as a potential factor in the progression of fibrosis in PBC patients.
Kim, Moon Young; Won, Chan Sik; Park, Hong Jun; Jeon, Hyo Keun; Hong, Hyun Il; Kim, Jae Woo; Kim, Hyun Soo; Kwon, Sang Ok; Kim, Jang Young; Yoo, Byung Su; Lee, Seung Hwan
Background/Aims The blunted ventricular systolic and diastolic contractile responses to physical and pharmacological stress in cirrhosis are termed cirrhotic cardiomyopathy (CCM). CCM has been known to involve multiple defects in the β-adrenergic signaling pathway. The aim of this study was to determine whether cirrhotic patients have blunted cardiac responses to catecholamine stimulation through dobutamine stress echocardiography (DSE). Methods Seventy-one cirrhotic patients with normal left ventricular (LV) chamber size and ejection fraction were enrolled. The LV systolic and diastolic functions were evaluated by two-dimensional and Doppler echocardiography at rest and during peak dobutamine infusion (40 µg/kg/min). An abnormal response was defined as a decrease of less than 10% in LV end-diastolic volume, a decrease of less than 20% in end-systolic volume, and an increase of less than 10% in LV ejection fraction (EF) at peak dobutamine infusion, based on previously used criteria. The early/late diastolic flow (E/A) ratio and diastolic parameters were also measured. Results A blunted LV response to dobutamine was observed in 18 of 71 cirrhotic patients (25.4%). The baseline EF was significantly higher in 18 patients with a blunted DSE response than that of those with a normal DSE response (P<0.05). The baseline and peak E/A ratios, which are common diastolic dysfunction markers, were higher in the cirrhosis group than in the control group (P<0.001). No adverse events associated with DSE were observed. Conclusions Blunted cardiac responses to dobutamine stimulation, which are implicated in defects in the β-adrenergic signaling pathway, might contribute to the pathogenesis of CCM in patients with cirrhosis. PMID:21415581
Nakanishi, Hiroyuki; Kurosaki, Masayuki; Tsuchiya, Kaoru; Nakakuki, Natsuko; Takada, Hitomi; Matsuda, Shuya; Gondo, Kouichi; Asano, Yu; Hattori, Nobuhiro; Tamaki, Nobuharu; Suzuki, Shoko; Yasui, Yutaka; Hosokawa, Takanori; Itakura, Jun; Takahashi, Yuka; Izumi, Namiki
We performed a prospective study to evaluate the ability of L-carnitine, which is involved in the β-oxidation of fatty acids, to reduce muscle cramps in patients with cirrhosis. Consecutive patients with cirrhosis and muscle cramps were given L-carnitine 300 mg, 3 times/day (900 mg/day, n = 19) or 4 times/day (1200 mg/day, n = 23) for 8 weeks. The frequency of muscle cramps was assessed by questionnaires, and the degree of muscle cramping was assessed by using the visual analogue scale (VAS). Muscle cramping was reduced in 88.1% of all subjects at the end of the 8-week study period and disappeared for 28.6% of patients. Overall VAS scores decreased significantly from 69.9 ± 22.5 at baseline to 26.2 ± 29.1 after 8 weeks (P < .0001). The dose of L-carnitine was significantly associated with percentages of patients with reduced muscle cramps after 8 weeks (43.5% in the 1200 mg/day group vs 10.5% in the 900 mg/day group, P = .037) and VAS scores at 8 weeks (9.9 ± 13.5 in the 1200 mg/day group vs 39.6 ± 31.9 in the 900 mg/day group, P = .003). No adverse events were reported. Therefore, L-carnitine appears to be safe and effective for reducing liver cramps in patients with cirrhosis.
King, Lindsay Y; Johnson, Kara B; Zheng, Hui; Wei, Lan; Gudewicz, Thomas; Hoshida, Yujin; Corey, Kathleen E; Ajayi, Tokunbo; Ufere, Nneka; Baumert, Thomas F; Chan, Andrew T; Tanabe, Kenneth K; Fuchs, Bryan C; Chung, Raymond T
Single nucleotide polymorphisms (SNPs) in the epidermal growth factor (EGF, rs4444903), patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409) genes, and near the interleukin-28B (IL28B, rs12979860) gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC) in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV)-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31-6.25) after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0-1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95%CI 0.96-3.35) for 2 unfavorable genotypes and 4.03 (95%CI 2.13-7.62) for unfavorable genotypes for all three loci (Ptrend<0.0001). In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression.
King, Lindsay Y.; Johnson, Kara B.; Zheng, Hui; Wei, Lan; Gudewicz, Thomas; Hoshida, Yujin; Corey, Kathleen E.; Ajayi, Tokunbo; Ufere, Nneka; Baumert, Thomas F.; Chan, Andrew T.; Tanabe, Kenneth K.; Fuchs, Bryan C.; Chung, Raymond T.
Single nucleotide polymorphisms (SNPs) in the epidermal growth factor (EGF, rs4444903), patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409) genes, and near the interleukin-28B (IL28B, rs12979860) gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC) in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV)-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31–6.25) after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0–1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95%CI 0.96–3.35) for 2 unfavorable genotypes and 4.03 (95%CI 2.13–7.62) for unfavorable genotypes for all three loci (Ptrend<0.0001). In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression. PMID:25504078
Bergamaschi, Cássia T.; Campos, Ruy R.
We tested the hypothesis that there is a topographical sympathetic activation in rats submitted to experimental cirrhosis. Baseline renal (rSNA) and splanchnic (sSNA) sympathetic nerve activities were evaluated in anesthetized rats. In addition, we evaluated main arterial pressure (MAP), heart rate (HR), and baroreceptor reflex sensitivity (BRS). Cirrhotic Wistar rats were obtained by bile duct ligation (BDL). MAP and HR were measured in conscious rats, and cardiac BRS was assessed by changes in blood pressure induced by increasing doses of phenylephrine or sodium nitroprusside. The BRS and baseline for the control of sSNA and rSNA were also evaluated in urethane-anesthetized rats. Cirrhotic rats had increased baseline sSNA (BDL, 102 vs control, 58 spikes/s; p<0.05), but no baseline changes in the rSNA compared to controls. These data were accompanied by increased splanchnic BRS (p<0.05) and decreased cardiac (p<0.05) and renal BRS (p<0.05). Furthermore, BDL rats had reduced basal MAP (BDL, 93 vs control, 101 mmHg; p<0.05) accompanied by increased HR (BDL, 378 vs control, 356; p<0.05). Our data have shown topographical sympathetic activation in rats submitted to experimental cirrhosis. The BDL group had increased baseline sSNA, independent of dysfunction in the BRS and no changes in baseline rSNA. However, an impairment of rSNA and HR control by arterial baroreceptor was noted. We suggest that arterial baroreceptor impairment of rSNA and HR is an early marker of cardiovascular dysfunction related to liver cirrhosis and probably a major mechanism leading to sympathoexcitation in decompensated phase. PMID:27055088
Villeneuve, J P; Condreay, L D; Willems, B; Pomier-Layrargues, G; Fenyves, D; Bilodeau, M; Leduc, R; Peltekian, K; Wong, F; Margulies, M; Heathcote, E J
The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are outweighed by serious side effects and by the risk of fatal exacerbation of disease activity. Lamivudine rapidly reduces hepatitis B virus (HBV)-DNA in serum to undetectable levels. We have treated 35 patients with chronic hepatitis B and decompensated cirrhosis with lamivudine 100 mg or 150 mg orally once daily. Pretreatment, all were positive for HBV-DNA in serum. Ten had Child-Pugh class B and 25 had Child-Pugh class C liver disease. Seven patients underwent liver transplantation within 6 months of treatment initiation, 5 patients died within 6 months, and 23 patients were treated for at least 6 months (mean = 19 months). In a majority of these 23 cases, there was a slow but marked improvement in liver function, which was most apparent after 9 months of treatment, with a decrease in serum bilirubin from 67 +/- 13 to 30 +/- 4 micromol/L (P <.05, baseline vs. 9 months), an increase in serum albumin from 27 +/- 1 to 34 +/- 1g/L (P <.05), and a decrease in Child-Pugh score from 10.3 +/- 0.4 to 7.5 +/- 0.5 (P <.05). Three patients developed resistance to lamivudine because of a mutation in the YMDD motif, but liver function did not deteriorate. We conclude that inhibition of viral replication with lamivudine results in a significant improvement of liver function in patients with decompensated HBV cirrhosis, but the long-term benefits remain uncertain.
Terés, J; Bordas, J M; Bru, C; Diaz, F; Bruguera, M; Rodes, J
The clinical data of 180 episodes of upper gastrointestinal bleeding in 168 patients with cirrhosis of the liver are examined. The source of bleeding had been determined by early endoscopy in all cases. In men under the age of 50 years, and without symptoms of liver failure, bleeding was due to ruptured gastro-oesophageal varices in 84% of cases. Severe liver failure was associated with acute lesions of gastric mucosa in many cases. No presumptive diagnosis of the source of haemorrhage could be based on the examination of other clinical data (presence of ascites, mode of presentation and pattern of bleeding, history of ulcer disease, alcoholism, and previous medication. PMID:1083824
Knot, E A; Drijfhout, H R; ten Cate, J W; de Jong, E; Iburg, A H; Kahlé, L H; Grijm, R
We describe the metabolism of purified human alpha 2-plasmin inhibitor in patients with liver cirrhosis to determine whether low plasma concentrations of alpha 2-plasmin inhibitor are the result of impaired synthesis or increased catabolism or both. A kinetic study was performed with 131I-alpha 2-plasmin inhibitor as a sensitive parameter of fibrinolysis in 14 patients with histologically proved liver cirrhosis compared with six healthy control subjects. Eight patients had macronodular cirrhosis (with positive hepatitis B surface antigen), and six had micronodular cirrhosis as a result of alcohol abuse. None of the patients had clinical signs of ascites, and in all the disease was stabilized. alpha 2-Plasmin inhibitor levels biologically and immunologically measured were decreased in all patients. Ten microCi 131I-alpha 2PI was injected intravenously, the disappearance of plasma radioactivity was measured, and turnover data were calculated according to the function x(t) = A1e-alpha 1t + A2e-alpha 2t + Be-beta t. Mean (+/- SD) turnover data in the control subjects were plasma radioactivity half-life 60.1 +/- 5.3 hours, fractional catabolic rate constant of the plasma pool 0.0318 +/- 0.0106 hr-1, and absolute catabolic (synthetic) rate constant 2.10 +/- 0.60 mg/kg/day. The alpha 1-phase was 1.26 +/- 0.23, and the transcapillary influx constant (k2,1) was 0.974 +/- 0.109 hr-1. In the patients, plasma radioactivity half-life was 58.7 +/- 12.09 hr, and fractional catabolic rate constant of the plasma pool 0.0283 +/- 0.0043 hr-1. The alpha 1-phase 4.74 +/- 6.48 and the transcapillary influx (k2,1) 3.08 +/- 3.9 hr-1 were both significantly increased compared with control values (p less than 0.05 and p less than 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Karlsen, Stine; Nielsen, Dennis Tønner; Grønbæk, Henning
Budd-Chiari syndrome (BCS) is a rare disease defined by congestive hepatopathy with obstruction of the hepatic venous outflow tract. Classical symptoms and signs include ascites, hepatomegaly, abdominal pain and various degrees of liver dysfunction. BCS is predominantly caused by thrombosis, malformations and venous compression. We present a case, in which BCS was the cause of liver cirrhosis complicated with refractory ascites and which can be misinterpreted as hepatocellular carcinoma nodules. The diagnosis was confirmed during the transjugular intrahepatic portosystemic shunt procedure with successful vascular stenting resolving the ascites formation.
Rada, Gabriel; Mac-Namara, Macarena
Ursodeoxycholic acid is considered as first line treatment in patients with primary biliary cirrhosis. Its mechanism of action in this disease is unknown and there is controversy about its clinical impact. Searching in Epistemonikos database, which is maintained by screening 19 databases, we identified four systematic reviews including 16 studies. We combined the evidence using tables with summary of findings following the GRADE approach and concluded ursodeoxycholic acid may not have any effect on pruritus, and there is uncertainty about its effect on mortality, need for liver transplantation or on any other important outcome for the patient.
Kim, Hee Yeon; Jang, Jeong Won
Estimating the prognosis of patients with cirrhosis remains challenging, because the natural history of cirrhosis varies according to the cause, presence of portal hypertension, liver synthetic function, and the reversibility of underlying disease. Conventional prognostic scoring systems, including the Child-Turcotte-Pugh score or model for end-stage liver diseases are widely used; however, revised models have been introduced to improve prognostic performance. Although sarcopenia is one of the most common complications related to survival of patients with cirrhosis, the newly proposed prognostic models lack a nutritional status evaluation of patients. This is reflected by the lack of an optimal index for sarcopenia in terms of objectivity, reproducibility, practicality, and prognostic performance, and of a consensus definition for sarcopenia in patients with cirrhosis in whom ascites and edema may interfere with body composition analysis. Quantifying skeletal muscle mass using cross-sectional abdominal imaging is a promising tool for assessing sarcopenia. As radiological imaging provides direct visualization of body composition, it is useful to evaluate sarcopenia in patients with cirrhosis whose body mass index, anthropometric measurements, or biochemical markers are inaccurate on a nutritional assessment. Sarcopenia defined by cross-sectional imaging-based muscular assessment is prevalent and predicts mortality in patients with cirrhosis. Sarcopenia alone or in combination with conventional prognostic systems shows promise for a cirrhosis prognosis. Including an objective assessment of sarcopenia with conventional scores to optimize the outcome prediction for patients with cirrhosis needs further research.
... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Indication of the presence of hepatitis B... presence of hepatitis B or cirrhosis. (a)(1) If the claimant or eligible surviving beneficiary is claiming... possessed by the state cancer or tumor registries, indicates the presence of hepatitis B or cirrhosis,...
... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Indication of the presence of hepatitis B or cirrhosis. 79.36 Section 79.36 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CLAIMS... § 79.36 Indication of the presence of hepatitis B or cirrhosis. Possible indication of hepatitis B...